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V Meininger

Publications and source records attributed to V Meininger.

At least 19 recordsLinked to original sources
PubMed1996

Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive disease with no effective treatment. In an initial study, riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients. We have carried out a double-blind, placebo-controlled, multicentre study to confirm those findings and to assess drug efficacy at different doses. METHODS: 959 patients with clinically probable or definite ALS of less than 5 years' duration were randomly assigned treatment with placebo or 50 mg, 100 mg, or 200 mg riluzole daily; randomisation was stratified by centre and site of disease onset (bulbar or limb). The primary outcome was survival without a tracheostomy. Secondary outcomes were rates of change in functional measures (muscle strength, functional status, respiratory function, patient's assessments of fasciculation, cramps, stiffness, and tiredness). The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat. Drug-effect on survival was assessed before (log-rank test) and after adjustment for known prognostic factors (Cox's model). FINDINGS: At the end of the study, after median follow-up of 18 months, 122 (50.4%) placebo-treated patients and 134 (56.8%) of those who received 100 mg/day riluzole were alive without tracheostomy (unadjusted risk 0.79, p = 0.076; adjusted risk 0.65, p = 0.002). In the groups receiving 50 mg and 200 mg riluzole daily, 131 (55.3%) and 141 (57.8%) patients were alive without tracheostomy (relative to placebo 50 mg adjusted risk 0.76, p = 0.04; 200 mg 0.61, p = 0.0004). There was a significant inverse dose response in risk of death. No functional scale discriminated between the treatment groups. The most common adverse reactions were asthenia, dizziness, gastrointestinal disorders, and rises in liver enzyme activities; they were commonest with the 200 mg dose. INTERPRETATION: Overall, efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio. This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1996

A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II.

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Superoxide dismutase activity in lymphoblastoid cells from motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients.

Point mutations in the gene encoding Cu,Zn superoxide dismutase (SOD1) are associated with autosomal dominant familial amyotrophic lateral sclerosis (FALS). We have measured Cu,Zn SOD activity in lymphoblastoid cells from affected and at risk FALS patients carrying mutations in the SOD1 gene, FALS patients without mutations in the SOD1 gene, individuals affected by the sporadic form of the disease (SALS), normal controls and individuals with other neurological abnormalities. The results show a significant decrease in Cu,Zn SOD activity in affected and at risk FALS individuals as compared to FALS patients without mutations, SALS individuals, normal and neurological controls. It is concluded that decreased SOD activity may contribute, together with other as yet unknown factors, to motor neurone demise.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Anti-sulfoglucuronyl paragloboside IgM antibodies in amyotrophic lateral sclerosis.

We report here our results on IgM anti-sulfated glucuronyl paragloboside (SGPG) antibodies in sera from patients with amyotrophic lateral sclerosis (ALS). Studies by enzyme linked immunosorbent assay on 72 ALS sera showed IgM polyclonal reactivity towards SGPG in 25 cases. The titer was high in 16 cases. Thin-layer chromatography immuno-overlay showed that reactivity with SGPG was associated to reactivity towards GM1 in five cases and to GM1 and GD1b in one case. Anti-SGPG reactivity was not found in controls and in multifocal motor neuropathy with conduction blocks, in contrast to anti-GM1 antibodies. The presence of anti-SGPG antibodies in ALS patients sera raise again the question of autoimmunity in this pathology.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Multifocal motor neuropathy with conduction block: a study of 24 patients.

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.

Adult↗
PubMed1995

Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, approximately 10% are inherited as an autosomal dominant trait. Mutations in the Cu/Zn superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases.

Amino Acid Sequence↗
PubMed1994

A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.

BACKGROUND: Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis. METHODS: To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days). RESULTS: After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantage with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlled period, but it remained significant in the overall population (P = 0.046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group. CONCLUSIONS: The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.

Adult↗
PubMed1994

Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons. The etiology of the majority of cases remains unknown. Recent findings from several laboratories suggest a role for neurofilaments in the development of motor neuron disorders. The C-terminal region of the human neurofilament heavy subunit (NEFH) contains a unique functional domain consisting of 43 repeat motifs of the amino acids Lys-Ser-Pro (KSP). This C-terminal region of NEFH forms the sidearm projections which cross-link the neurofilaments. Previously, we have demonstrated polymorphism in the C-terminal region of the human NEFH: an allelic variant of a slightly larger molecular size, containing an additional KSP phosphorylation motif. Novel mutations in this region were found in five ALS patients. We propose that changes in the KSP-repeat domain may affect the cross-linking properties of the heavy neurofilament subunit and perhaps contribute to the development of neurofilamentous swellings in motor neurons, a hallmark of ALS.

Aged↗
PubMed1994

[Effect of naftidrofuryl (LS129) on axonal growth].

The response of growing axons and microtubules to naftidrofuryl (LS 129) was investigated in vitro and in situ in the embryonic nervous system of mice. For this purpose, we used rotatory cultures of post-implanted embryos in a rat or human serum containing the compound combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene-glycol embedded semithin sections. We also analysed the protective effect of naftidrofuryl to treatment with vinka alkaloids using the same method. After culture in rat serum enriched with naftidrofuryl at concentration of 20 microM and above, we observed an increase of both the number of axonal profiles in semithin sections and of the number of microtubules per surface unit in electron micrographs. After culture in human serum obtained from an healthy volunteer after a unique intake of naftidrofuryl at 900 mg/j and above, we observed the same effect of an increasing of the number of axonal profiles in the tectal plate of mice embryos in semithin sections. These results suggest a promoting effect of naftidrofuryl on axonal growth and on microtubules' assembly. They suggest a therapeutic effect of this drug at daily doses of 900 mg/j. After culture in a rat serum enriched with naftidrofuryl at concentration of 20 microM, we observed a protective effect of this drug toward the disruption of axonal microtubules by vinka alkaloids. This effect seems rather specific since we did not observe the same protection toward the mitotic microtubules. These results suggest that naftidrofuryl could be used to prevent the neurological side effects of vinka alkaloids.

Animals↗
PubMed1993

Androgen receptor gene polymorphisms in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is more common in men than in women (male to female ratio of approximately 2:1), suggesting a role for a sex-linked factor in the disease. The recent identification of a mutation of the androgen receptor gene in Kennedy's disease or X-linked bulbospinal neuronopathy, a rare form of progressive lower motor neurone degeneration, also associated with clinical signs of androgen insensitivity, raises the possibility that androgen function may be disturbed in other motor neurone disorders, including ALS. The Kennedy's disease mutation consists of an increased size of a highly polymorphic CAG repeat sequence in the first exon of the androgen receptor gene, coding for a polyglutamine tract. We have analysed this CAG repeat sequence in a large number of patients with typical sporadic ALS and in normal controls, in order to test the hypothesis that this polymorphism of the androgen receptor gene may influence susceptibility for ALS. We report that the distribution of alleles relating to the size of the CAG repeat sequence of the androgen receptor gene is similar in ALS and controls, indicating that polymorphisms of the CAG repeat sequence of the androgen receptor gene play a limited role, if any, in susceptibility to ALS.

Alleles↗
PubMed1993

Breaking bad news in amyotrophic lateral sclerosis.

There are many difficulties of communication with patients with amyotrophic lateral sclerosis (motor neurone disease). In France, most physicians have a policy of keeping the fact of this diagnosis from both patients and relatives. This paper describes an alternative approach based on open communication, and applies that principle to handling issues of communication associated with various aspects of four different topics: the diagnosis itself, the development of handicap, swallowing difficulties, and respiratory difficulties.

Amyotrophic Lateral Sclerosis↗
PubMed1992

Antiganglioside antibodies in motor-neuron diseases and peripheral neuropathies: study by ELISA technique and immunodetection on thin-layer chromatography.

We report here our studies on IgM reactivity towards peripheral nervous system gangliosides, in motor-neuron diseases (MND) without IgM gammopathies, and in peripheral neuropathies with IgM gammopathies. We showed by enzyme linked immunosorbent assay technique, that anti-GM1 IgM antibodies were often present at a low level in normal controls in contrast to anti-GD1b antibodies, which were never detected in control sera. We evidenced that several steps of the ELISA technique were critical such as the nonaddition of detergent in buffer solutions used for dilutions and for washing and the choice of the ELISA plates. We studied 50 cases of motor-neuron diseases, among which 40 typical cases of Amyotrophic Lateral Sclerosis, only a few had high anti-GM1 antibodies levels, which were always confirmed by immunodetection on thin-layer chromatography. These antibodies were generally directed against the oligosaccharide epitope present also in asialoGM1. No correlation has been as yet established in relation to the clinical state of the patients. In a few cases of polyneuropathies associated with IgM gammopathies, antiganglioside antibodies have been reported. We have found anti-GD1b antibodies to be present in a sensory-motor axonal neuropathy; axonal involvement was evidenced by electrophysiological study.

Autoantibodies↗
PubMed1991

Modifications of tubulin heterogeneity during embryonic and postnatal stages in a specific region of mouse brain.

An auditory nucleus (the inferior colliculus of the mouse) was used to study the modifications of the heterogeneity of tubulin which occur at various stages of development and maturation. Both the cold-stable (CS) and cold-labile (CL) fractions of tubulin were analyzed by high-resolution isoelectric focusing. Our results suggest that tubulin heterogeneity is modified at critical stages of development and maturation, with specific variations of the two fractions. Stage E10 corresponding to the appearance of the first young neurons and axonal profiles is marked by the modification of the CS fraction with the emergence of isotypes alpha 5 to alpha 8 and beta 12 and beta 17. Stage E12 is characterized by the modifications of the CL fraction, particularly the beta-group; at this stage the first dendrites become visible. At birth, all isotypes increase in both the CL and CS fractions. At stages P7-P10 transient modifications of a group of both CS and CL fractions and of the beta group of CS fraction occur. These are associated with the emergence of isotypes beta 17 to beta 20 in the CL fraction. This period precludes the initial period of functional maturation of the auditory system which occurs from P10 to P20. During this period, the CL fraction (alpha and beta group) remains unmodified, whereas all isotypes of the CS fraction, except 3-4, display complex variations with an initial decrease until P12, an increase until P17, and a final decrease until P20.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Comparative anatomy and histology of the radial artery and the internal thoracic artery. Implication for coronary artery bypass.

Anatomical characteristics of the radial a. were compared to those of the internal thoracic a., considered as a gold standard in coronary surgery. The length, the diameter, the collateral distribution and the wall thickness of these two arteries were studied comparatively. In addition, a comparative histological analysis was carried out. Anatomical and histological characteristics of these two arteries have important implications for coronary artery bypass.

Angiography↗
PubMed1991

Quantitative analysis of monoclonal immunoglobulins in serum of patients with amyotrophic lateral sclerosis.

In a prospective study, we analysed the presence of monoclonal immunoglobulin (moIg) in the serum from 30 patients with amyotrophic lateral sclerosis (ALS) and 30 matched controls using a sensitive Western blot technique. The incidence of serum moIg was 60% in the ALS group and 13.3% in the control group. Most ALS sera contained 2 or 3 monoclonal components. They were IgG (72.7%) and IgM (27.3%). These results corroborate the concept of a probable association between ALS and serum moIg.

Adolescent↗
PubMed1991

[Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis].

Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.

Adult↗