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S Marchand

Publications and source records attributed to S Marchand.

At least 19 recordsLinked to original sources
PubMed2003

Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, system disease. It commonly affects the small peripheral joints (such as fingers and wrist). The main goals of intervention for RA are preventing joint deformity, preserving joint function, and reducing inflammation and pain. Transelectrical nerve stimulation (TENS) is a form of electrotherapy and is thought to produce analgesia according to the gate control theory. OBJECTIVES: To determine the efficacy and safety of TENS in the treatment of RA of the hand. The primary outcomes of interest were relief of grip pain and resting pain intensity, relief of joint tenderness, number of tender joints and patient assessment of disease. The secondary objective was to determine the most effective mode of TENS application in pain control. SEARCH STRATEGY: We searched for relevant studies, in English, in the Cochrane field of physical and related therapies, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, HEALTHSTAR, Sports Discus, CINAHL, Current Contents, and the PEDro database, up to October 2002. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Study results were extracted by two independent reviewers. Continuous outcomes were analyzed by weighted mean difference (WMD) using a fixed effects model. MAIN RESULTS: Three RCTs, involving 78 people, were included in this review. AL-TENS and C-TENS were compared to placebo and to each other. Administration of 15 minutes of AL-TENS a week, for 3 weeks, resulted in a significant decrease in rest pain (67% relative benefit, 45 points absolute benefit on 100 mm VAS scale) but not in grip pain compared to placebo. AL-TENS did result in a clinical beneficial improvement in muscle power scores with a relative difference of 55%, and an absolute benefit of 0.98, compared to placebo. No significant difference was found between one 20-minute treatment duration of C-TENS versus AL-TENS, or C-TENS versus placebo on decrease in mean scores for rest pain or grip pain, or on the number of tender joints. Results showed a statistically significant reduction in joint tenderness, but no clinical benefit from C-TENS over placebo in relief of joint tenderness. No statistically significant difference was shown between 15 days of treatment with C-TENS or AL-TENS in relief of joint pain, although there was a clinically important benefit of C-TENS over AL-TENS on patient assessment of change in disease (risk difference 21%, NNT 5). REVIEWER'S CONCLUSIONS: There are conflicting effects of TENS on pain outcomes in patients with RA. AL-TENS is beneficial for reducing pain intensity and improving muscle power scores over placebo while, conversely, C-TENS resulted in no clinical benefit on pain intensity compared with placebo. However C-TENS resulted in a clinical benefit on patient assessment of change in disease over AL-TENS. More well designed studies with a standardized protocol and adequate number of subjects are needed to fully conclude the effect of C-TENS and AL-TENS in the treatment of RA of the hand.

Arthritis, Rheumatoid↗
PubMed2002

Convulsant and subconvulsant doses of norfloxacin in the presence and absence of biphenylacetic acid alter extracellular hippocampal glutamate but not gamma-aminobutyric acid levels in conscious rats.

Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents. The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively. This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus. Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations. Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures. These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations. Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior. In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h. In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA.

Administration, Oral↗
PubMed2001

Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy.

OBJECTIVE: Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene. METHODS: Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively. RESULTS: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9 years. CONCLUSION: This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.

Adolescent↗
PubMed2001

Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene.

BACKGROUND: Tibial muscular dystrophy (TMD), a late-onset dominant distal myopathy, is caused by yet unknown mutations on chromosome 2q, whereas MD with myositis (MDM) is a muscular dystrophy of the mouse, also progressing with age and linked to mouse chromosome 2. For both disorders, linkage studies have implicated titin as a potential candidate gene. METHODS: The authors analyzed major candidate regions in the titin gene by sequencing and Southern blot hybridization, and performed titin immunohistochemistry on TMD patient material to identify the underlying mutation. Western blot studies were performed on the known titin ligands in muscle samples of both disorders and controls, and analysis of apoptosis was also performed. RESULTS: The authors identified almost complete loss of calpain3, a ligand of titin, in the patient with limb-girdle MD (LGMD) with a homozygous state of TMD haplotype when primary calpain3 gene defect was excluded. Apoptotic myonuclei with altered distribution of transcription factor NF-kB and its inhibitor IkBalpha were encountered in muscle samples of patients with either heterozygous or homozygous TMD haplotype. Similar findings were confirmed in the MDM mouse. CONCLUSIONS: These results imply that titin mutations may be responsible for TMD, and that the pathophysiologic pathway following calpain3 deficiency may overlap with LGMD2A. The loss of calpain3 could be a downstream effect of the deficient TMD gene product. The significance of the secondary calpain3 defect for the pathogenesis of TMD was emphasized by similar calpain3 deficiency in the MDM mouse, which is suggested to be a mouse model for TMD. Homozygous mutation at the 2q locus may thus be capable of producing yet another LGMD.

Animals↗
PubMed2001

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Adult↗
PubMed2001

Ventricular and parenchymal surface before and after shunting--do they have prognostic value for outcome?

PATIENTS AND METHODS: 26 consecutive patients with early hydrocephalus (median age at shunting 2.5 months) were followed up to the age of 3 years, prospectively. The work-up included: regular evaluation of psychomotor development and CT/MRI prior and 6 months following surgery. The latter with measurement of the area of the ventricles (degree of hydrocephalus) and the area of the hemispheres in cm(2) (area of hemispheres minus area of ventricles = parenchymal area and degree of brain mass) at the level of the slice with the largest area of the ventricles. RESULTS: 16 (62 %) had normal development (= Group A) and 10 (38 %) moderate or severe retardation (= Group B). The mean ventricular surface was 25.4 cm(2) in Group A and 31.2 cm(2) in Group B prior to surgery (p = 0.1) and 8.9 versus 14.1 cm(2) postsurgery (p = 0.2). The percentage decrease postoperatively was 59.9, versus 57.1 % (p = 0.4). The percentage of ventricular surface in relation to the hemispheres prior to surgery was 42.2 versus 51.4 % (p = 0.1) and post-surgery 12.8 versus 22.4 % (p = 0.1). The mean parenchymal surface was 34.9 cm(2) in Group A and 29.0 cm(2) in Group B prior to surgery (p = 0.3) and 60.9 versus 48.1 cm(2) post surgery (p = 0.07). Percentage increase was 87.3 % versus 77.3 % (p = 0.9). The absolute increase was 26.0 versus 19.0 cm(2) postoperatively (p = 0.2). In contrast to these mean values and their distribution with no significant differences in Group A and B there was some correlation between development and percentage of ventricular surface in relation to the hemispheres prior to surgery: more than 40 % is a critical value, because most of the later retarded children belonged to this radiological subgroup and only half of the later normal patients. After surgery, there was a distinct correlation between developmental outcome and parenchymal surface and its absolute increase in cm(2): most of those who had a normal outcome had a parenchymal surface of more than 40 cm(2) in the third trimenon and an increase of 20 cm(2) and more within six months post surgery, whereas this was the case in only 40 - 50 % of the retarded patients. CONCLUSIONS: In most young infants with hydrocephalus there is more brain mass than the ventricular enlargement suggests. The prognostic value of quantitative evaluation of neuroimaging should not be overestimated. Nevertheless, some prognostication in this age group is possible prior to surgery by measurement of ventricular area in relation to the hemispheres and after surgery by measurement of the parenchymal area and its increase in cm(2).

Cerebral Ventricles↗
PubMed2001

Cortical activation by tactile and painful stimuli in hemispherectomized patients.

Hemispherectomized patients are able to perceive tactile and painful stimuli on their nonparetic as well as paretic body halves. We have used functional MRI to study the cortical mechanisms underlying this preserved somatosensory capacity. Nonpainful brushing and painful heat were applied to the skin of the legs in four hemispherectomized patients and, for comparison, in four normal subjects. Cortical activation was studied with a 1.5 T scanner using a BOLD (blood oxygen level dependent) protocol. All patients rated both the brushing and the heat pain as almost equally intense on each leg and the ratings were similar to those in normals. Brushing on the nonparetic leg activated primary and secondary somatosensory cortices (S1 and S2) in all patients, similar to findings in normals. Brushing on the paretic leg activated S1 in two patients and S2 in one of these patients. Heat pain activated S2, insular cortex and anterior cingulate cortex to a similar degree for both legs, but the activation was weaker in the patients than in the normals. For the individual patient, there was generally no obvious correlation between cortical activation as studied with the BOLD technique and psychophysical performance. The findings from tactile stimulation of the nonparetic leg, that the activation was similar to the contralateral activation in normals, suggest that tactile information processing in the hemisphere contralateral to the stimulation is independent of the corpus callosum. In contrast, the pain activation for the nonparetic leg was weaker than in normals, suggesting that pain activation in the hemisphere contralateral to the stimulation is dependent on transcallosal information processing. The latter finding was corroborated by a subnormal capacity for pain localization on the nonparetic foot in two of the patients. The findings from stimulation of the paretic leg show that areas typically involved in the processing of tactile and painful stimuli can be activated by ipsilateral pathways directly from the periphery. The tactile-evoked ipsilateral S1 activation may be due to subcortical reorganization, since it was not observed in the normal subjects.

Adult↗
PubMed2001

A pharmacokinetic/pharmacodynamic approach to show that not all fluoroquinolones exhibit similar sensitivity toward the proconvulsant effect of biphenyl acetic acid in rats.

The proconvulsant effect of biphenyl acetic acid (BPAA) on several fluoroquinolones (FQs) was investigated in vivo, by measuring drug concentrations in the biophase at the onset of convulsions. Male Sprague-Dawley rats (n = 134) were given BPAA orally, at various doses 1 h before starting FQ infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for drug concentration determination. The FQ-BPAA interactions in the biophase (CSF) were adequately described on most occasions by an inhibitory Emax effect model with a baseline effect parameter. The efficacy of the proconvulsant effect was characterized by the ratio of the CSF concentrations of FQs at the onset of convulsant activity when BPAA was absent (CCSF0, FQs) and as BPAA CSF concentrations tended toward infinity (CCSFbase, FQs). This ratio varied from 15 for enoxacin to 1.9 for sparfloxacin. The potency of the proconvulsant effect was characterized by the CSF concentration of BPAA corresponding to a proconvulsant effect half of its maximum. This parameter varied between 0.18 +/- 0.06 micromol/L with enoxacin and 15.0 +/- 12.1 micromol/L with sparfloxacin. The CSF diffusion of all FQs was apparently non-linear, as well as the plasma protein binding of BPAA, complicating interpretation of plasma data. The important variability in the proconvulsant effect of BPAA demonstrated in this study between various FQs suggests that in vitro gamma-aminobutyric acid (GABA) binding experiments conducted in the presence of BPAA are unlikely to be good predictors of FQ convulsant risk in clinical practice.

Animals↗
PubMed2001

Hypoxic vasoconstriction of rat main pulmonary artery: role of endogenous nitric oxide, potassium channels, and phosphodiesterase inhibition.

This study investigated the influence of NO, potassium (K+) channel blockade, and the phosphodiesterase inhibitors (PDEIs) theophylline (non-selective PDEI), siguazodan (PDE3I), rolipram (PDE4I), and zaprinast (PDE5I) on rat isolated main pulmonary artery hypoxic (95% N2 and 5% CO2) vasoconstriction. Hypoxic vasoconstriction increased by 27% (p < 0.01) in the presence of the NO synthase inhibitor L-NAME (10(-4) M), and by 15% (p < 0.05) in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M), without potentiation by the combination of these two drugs. Hypoxic vasoconstriction decreased by 28% (p < 0.01) in presence of the Kv,-voltage-dependent channel blocker 4-aminopyridine (10(-3) M), whereas the other K+ channel blockers, charybdotoxin (BKCa, large-conductance Ca2+-sensitive K+ channels) and apamin (SKCa, small-conductance Ca2+-sensitive K+ channels) had no effect. The nonselective PDEI theophylline induced a concentration-dependent relaxation (pD2 = 4.05, Emax = 90% [expressed as a percentage of maximal relaxation induced by papaverine 10(-4) M]). Among the selective PDEIs, siguazodan was significantly (p < 0.01) more efficient than rolipram and zaprinast (Emax values were 84%, 67%, and 58%, respectively) and significantly (p < 0.05) more potent than zaprinast (pD2 values were 6.48, 6.34, and 6.16 for siguazodan, rolipram, and zaprinast). Glibenclamide and L-NAME significantly (p < 0.05) shifted the concentration-response curve (CRC) for zaprinast to the right, and L-NAME shifted the CRC significantly to the right for siguazodan. In the presence of L-NAME, glibenclamide had no effect on the CRC of zaprinast. We conclude that (a) NO exerts a permanent inhibitory effect against hypoxic vasoconstriction that might be mediated in part by an activation of K(ATP) channels; (b) a 4-aminopyridine-sensitive K+ channel is involved in vasoconstriction under hypoxic conditions; (c) PDEs 3 and 5 are the predominant PDE isoforms in rat pulmonary artery relaxation; and (d) NO and K(ATP), but neither BK(Ca), SK(Ca), nor Kv channels, are involved in the relaxant effect of PDEIs.

Animals↗
PubMed2001

Calpain 3 mRNA expression in mice after denervation and during muscle regeneration.

Lack of functional calpain 3 in humans is a cause of limb girdle muscular dystrophy, but the function(s) of calpain 3 remain(s) unknown. Special muscle conditions in which calpain 3 is downregulated could yield valuable clues to the understanding of its function(s). We monitored calpain 3 mRNA amounts by quantitative RT-PCR and compared them with those of alpha-skeletal actin mRNA in mouse leg muscles for different types of denervation and muscle injury. Intact muscle denervation reduced calpain 3 mRNA expression by a factor of 5 to 10, while alpha-skeletal actin mRNA was reduced in a slower and less extensive manner. Muscle injury (denervation-devascularization), which leads to muscle degeneration and regeneration, induced a 20-fold decrease in the mRNA level of both calpain 3 and alpha-skeletal actin. Furthermore, whereas in normal muscle and intact denervated muscle, the full-length transcript is the major calpain 3 mRNA, in injured muscle, isoforms lacking exon 6 are predominant during the early regeneration process. These data suggest that muscle condition determines the specific calpain 3 isoform pattern of expression and that calpain 3 expression is downregulated by denervation.

Actins↗
PubMed2001

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polarization immunoassay (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/-SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine. Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

Administration, Inhalation↗
PubMed2001

Differential targeting of components of the dystrophin complex to the postsynaptic membrane.

Accumulating evidence points to the participation of dystroglycan in the clustering of nicotinic acetylcholine receptors at the neuromuscular junction [Côté et al. (1999) Nature Genet., 3, 338--342]. Dystroglycan is part of a multimolecular complex, either associated with dystrophin (the dystrophin-associated protein complex) at the sarcolemma or with utrophin (the utrophin-associated protein complex) at the neuromuscular junction. Understanding the assembly of this complex at the developing synapse led us to investigate, in Torpedo electrocyte, the intracellular routing and the targeting of several of its components, including dystroglycan, syntrophin, dystrophin and dystrobrevin. We previously demonstrated that acetylcholine receptors and rapsyn, the 43-kDa receptor-associated protein at the synapse, are cotargeted to the postsynaptic membrane via the exocytic pathway [Marchand et al. (2000) J. Neurosci., 20, 521--528]. Using cell fractionation, immunopurification and immuno-electron microscope techniques, we show that beta-dystroglycan, an integral glycoprotein that constitutes the core of the dystrophin-associated protein complex localized at the innervated membrane, is transported together with acetylcholine receptor and rapsyn in post-Golgi vesicles en route to the postsynaptic membrane. Syntrophin, a peripheral cytoplasmic protein of the complex, associates initially with these exocytic vesicles. Conversely, dystrophin and dystrobrevin were absent from these post-Golgi vesicles and associate directly with the postsynaptic membrane. This study provides the first evidence for a separate targeting of the various components of the dystrophin-associated protein complex and a step-by-step assembly at the postsynaptic membrane.

Animals↗
PubMed2001

[Home chemotherapy].

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Antineoplastic Agents↗
PubMed2000

Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice.

Calpain 3 is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. It was previously shown that defects in the human calpain 3 gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly the proximal limb muscles. To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we generated capn3-deficient mice by gene targeting. capn3-deficient mice are fully fertile and viable. Allele transmission in intercross progeny demonstrated a statistically significant departure from Mendel's law. capn3-deficient mice show a mild progressive muscular dystrophy that affects a specific group of muscles. The age of appearance of myopathic features varies with the genetic background, suggesting the involvement of modifier genes. Affected muscles manifest a similar apoptosis-associated perturbation of the IkappaBalpha/nuclear factor kappaB pathway as seen in LGMD2A patients. In addition, Evans blue staining of muscle fibers reveals that the pathological process due to calpain 3 deficiency is associated with membrane alterations.

Animals↗
PubMed2000

The torpedo electrocyte: a model system to study membrane-cytoskeleton interactions at the postsynaptic membrane.

Many aspects of the organization of the electromotor synapse of electric fish resemble the nerve-muscle junction. In particular, the postsynaptic membrane in both systems share most of their proteins. As a remarquable source of cholinergic synapses, the Torpedo electrocyte model has served to identify the most important components involved in synaptic transmission such as the nicotinic acetylcholine receptor and the enzyme acetylcholinesterase, as well as proteins associated with the subsynaptic cytoskeleton and the extracellular matrix involved in the assembly of the postsynaptic membrane, namely the 43-kDa protein-rapsyn, the dystrophin/utrophin complex, agrin, and others. This review encompasses some representative experiments that helped to clarify essential aspects of the supramolecular organization and assembly of the postsynaptic apparatus of cholinergic synapses.

Animals↗
PubMed2000

The myristoylated protein rapsyn is cotargeted with the nicotinic acetylcholine receptor to the postsynaptic membrane via the exocytic pathway.

Rapsyn, a 43 kDa protein required to cluster nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction, is tightly associated with the postsynaptic membrane via an N-terminal myristoylated site. Recent studies have shown that some acylated proteins associate with the exocytic pathway to become targeted to their correct destination. In this work, we used Torpedo electrocyte to investigate the intracellular routing of rapsyn compared to those of AChR and Na,K-ATPase, the respective components of the innervated and noninnervated membranes. We previously demonstrated that these latter two proteins are sorted and targeted to plasma membrane via distinct populations of post-Golgi vesicles (). Biochemical and immunoelectron microscopy analyses of various populations of post-Golgi vesicles immunopurified with magnetic beads led us to identify post-Golgi transport vesicles containing both rapsyn and AChR. These data suggest that rapsyn, as for AChR, specifically follows the exocytic pathway. Furthermore, immunogold-labeling experiments provided in situ evidence that AChR and rapsyn are cotransported in the same post-Golgi vesicles. Taken together, our observations suggest that rapsyn and AChR are cotargeted to the postsynaptic membrane.

Animals↗