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Biomedical subjects

B Dubois

Publications and source records attributed to B Dubois.

At least 37 records · Page 2Linked to original sources
PubMed2005

Polymorphisms in the interleukin-4 and IL-4 receptor genes and multiple sclerosis: a study in Spanish-Basque, Northern Irish and Belgian populations.

Cytokine gene polymorphisms are known to influence susceptibility and disease course of many autoimmune diseases. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. We analysed both the well-known intronic variable number of tandem repeat (VNTR) and +33 C/T single-nucleotide polymorphisms (SNP) in the IL-4 gene, as well as the functional Q551R SNP in the IL4-R gene in a cohort of three distinct populations comprising sporadic cases and controls from the northern Spanish Basque Country and Northern Ireland, as well as family trios from Belgium. The IL-4 +33 TT genotype was decreased in primary progressive (PP) versus relapsing-remitting (RR) patients in the Northern Irish population (OR = 0.14; 95% CI = 0.018-1.09). Two-marker haplotype distribution of the VNTR and +33 C/T SNP in PP patients differed from that seen in RR patients in Northern Ireland (P = 0.03). The R allele of the Q551R SNP was significantly under-transmitted in the Belgian trio families (P = 0.003), although this effect was not seen in the Northern Irish and Basque data sets. We did not identify IL-4-IL4-R gene-gene interaction in determining susceptibility or clinical parameters of MS. Disease or genetic heterogeneity or both may be responsible for the observed lack of reproduction in different populations. Our data reinforce recent findings for a role of IL4-R in susceptibility to MS.

Adult↗
PubMed2005

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

OBJECTIVE: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. METHODS: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). RESULTS: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. CONCLUSIONS: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.

Antiparkinson Agents↗
PubMed2004

Specific cerebral networks for maintenance and response organization within working memory as evidenced by the 'double delay/double response' paradigm.

Most of the working memory (WM) tasks used in functional imaging studies are based on the principle of the delayed response in which both the storage and the response organization are present during the delay period. It is therefore difficult to isolate activation specific to the storage function from that specific to the organization of the response. To determine the specific neural networks associated with these two WM operations, we performed a functional MRI study in healthy subjects using a new paradigm, 'the double delay/double response' tasks. This paradigm isolates maintenance from response organization by dividing the delay into two separate parts, the first being dedicated to memory, while the second includes response organization. Activation within the dorsolateral prefrontal cortex (DLPFC) followed a relative hemispheric dissociation: activation related to maintenance was predominant in the right DLPFC but was only detected when the load exceeded three items. Activation related to response organization was predominant in the left DLPFC, regardless of whether this response was based on information held in WM ('memory guided') or was independent of WM ('visually-guided'). These results suggest that activation of the DLPFC, should be interpreted in terms of executive processing for both maintenance and response organization.

Adult↗
PubMed2004

Motor signs during the course of Alzheimer disease.

BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. OBJECTIVE: To describe the progression and identify predictors of individual MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

Aged↗
PubMed2004

Pixantrone (BBR2778): a new immunosuppressant in multiple sclerosis with a low cardiotoxicity.

Mitoxantrone (MX) has been approved by the Food and Drug Administration for the treatment of rapidly progressive multiple sclerosis (MS). Unfortunately, its long-term administration is prevented by the cardiotoxicity. Pixantrone (PIX) is an analogue of MX devoid of toxic effects on cardiac tissue and was developed as a replacement for other anthracenediones in cancer patients. With a view to an application in MS patients, experimental data demonstrated that PIX is as potent as MX in preventing acute experimental allergic encephalomyelitis development as well as the occurrence of relapses in the chronic model. Safety data from animal studies and from phase II trials in cancer patients confirm a very weak cardiotoxicity, if any. A phase I trial with PIX in patients with a rapidly progressive MS seems thus warranted.

Animals↗
PubMed2004

[Dysexecutive syndromes and degenerative diseases].

A dysexecutive syndrome is observed not only in frontotemporal lobar degeneration, but also in subcortical degenerative diseases, and even in Alzheimer's disease whose lesions predominate in temporoparietal associative areas. The association between a dysexecutive syndrome and various cerebral localisations may be explained by the fact that cognitive and behavioral organisation recruits anatomofunctional frontostriatal and frontoparietal circuits. Both animal experimentation and human clinical observation argue in favour of a functional continuity and complementarity among these loops. The prefrontal cortex would be particularly needed in new situations, to inhibit old programs of action not adapted to the present context and to elaborate new ones; the basal ganglia would be rather required by the repetition of the situation to progressively transform the new program in routine. If we refer to Shallice model, we can hypothesize that optimal executive functions require the preservation not only of the Supervisory Attentional System, mainly dependent on the prefrontal cortex, but also of the Contention Scheduling, recruiting the basal ganglia, and of the Schemas of Action, represented in parietal and premotor areas. Therefore, the neuropsychological assessment of patients with degenerative diseases contributes to the understanding of the anatomofunctional architecture of executive functions.

Basal Ganglia↗
PubMed2003

Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization.

BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.

Adrenal Cortex Hormones↗
PubMed2003

The prefrontal cortex and conscious monitoring of action: an experimental study.

To investigate the role of the prefrontal cortex in conscious monitoring, we used an experimental paradigm generating a conflict between the action planned and the sensory-motor feedback. We analyzed the acquisition of explicit knowledge of the strategy for resolving the conflict and its influence on motor adaptation. Twenty patients with frontal lobe lesions and 18 controls had to trace a sagittal line with a stylus on a graphics tablet. A mirror on which the traced line, processed by a computer, was projected hid the hand. A mask limited visual feedback to the last third of the trajectory. Without informing the subjects, the line traced was modified by introducing a bias of 24 degrees to the right. To succeed in the task, subjects had to modify their motor program and to deviate their trajectory in the opposite direction. Conscious elaboration of the strategy was evaluated by the number of trials needed to explicitly report the required deviation. Three groups of patients were distinguished: (1). with normal explicit strategy; (2). with delayed explicit strategy, and (3). without explicit strategy at the last trial. They significantly differed by the severity of the dysexecutive syndrome, particularly of environmental adherence. Motor adaptation was evaluated by the area between the line traced and the ideal line to compensate for the deviation. In patients with normal elaboration of the strategy, motor control was similar to that of controls, but it was severely disturbed in the other two groups. These results suggest the involvement of the prefrontal cortex in conscious motor monitoring.

Adaptation, Physiological↗
PubMed2003

Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease.

The protein flotillin-1 is associated with the 'lipid rafts', that is, membrane microdomains that are enriched in cholesterol and sphingolipids. We compared flotillin-1 immunoreactivity in the hippocampus, amygdala and isocortex (Brodmann area 22) of six controls and 13 Alzheimer's disease (AD) cases (10 sporadic and three familial). A diffuse labelling of the neuropil was observed in most of the samples. The intensity of this labelling was not correlated with the density of neurofibrillary tangles (NFT) or of senile plaques. Some neuronal cell bodies were diffusely labelled in patients as in controls. Immunostained granular bodies were found in the cell body of a few neurones. The density of neuronal profiles containing large granular bodies (diameter > or =2 microm) was significantly higher in AD cases and was correlated with the density of NFTs in the three regions that were studied. Sections stained by double immunofluorescence methods and examined with confocal microscopy suggested that flotillin-1 accumulated most often in tangle-bearing neurones (76% of flotillin-1-positive neurones contained a NFT). Flotillin-1 immunoreactivity, even when found in a tangle-bearing neurone, was not colocalized with tau protein indicating that the two proteins were not in close contact and probably in different subcellular compartments. Flotillin-1-positive granular bodies were also found in neurones containing Pin1-positive vesicles but were not colocalized with them. Flotillin-1 immunoreactivity was colocalized with cathepsin D, a lysosomal marker. These data indicate that flotillin-1, a marker of rafts, accumulates in lysosomes of tangle-bearing neurones in the course of AD.

Aged↗
PubMed2003

[Neuropsychological evaluation can contribute to the diagnosis of movement disorders].

Neurodegenerative diseases of the extrapyramidal system can be difficult to identify, particularly those with discrete symptoms or a non-specific or polymorphous complex motor expression. Nevertheless, most of the patients with these diseases present a particular cognitive pattern so the neuropsychological evaluation can contribute significantly to diagnosis. Progressive supranuclear palsy, corticobasal degeneration, Huntington's disease, and Lewy body dementia can be easily identified on the basis of their distinctive motor and cognitive features. Clinical manifestations may be less specific in other diseases such as striatonigric degeneration or idiopathic Parkinson's disease. We present here the characteristic neuropsychological features of each of these diseases and their contribution to diagnosis.

Basal Ganglia Diseases↗
PubMed2003

[Prevention of chronic renal failure in the adult].

Chronic renal failure is an unrecognised disease, with an insidious and rather silent development, for which the general practitioners are too often passive. This review would like to insist on the detection of people at risk or with early abnormalities, on the optimal guidelines to slowdown the evolution to more severe and irreversible stages, on the prevention of uremic and cardiovascular complications and on the preparation to end stage renal treatments.

Adult↗
PubMed2002

["The 5 words": a simple and sensitive test for the diagnosis of Alzheimer's disease].

OBJECTIVE: Alzheimer's disease (AD) is under-diagnosed in France. Today only an estimated 50% of patients are identified. Diagnosis of AD is particularly difficult because the amnesic syndrome, characteristic of the disease, is often confused with memory dysfunction that is frequent during the process of aging. The improvement in the diagnostic conditions of AD relies on the availability of a simple and reliable tool for screening memory disorders of organic origin. METHOD: The 5-word test studies the recall of a short list, which the physician ensures the patient has registered. Its construction permits the identification of patients exhibiting objective memory disorders. A validation study has been conducted in 86 patients suffering from AD and 126 persons complaining of functional memory disorders. RESULTS: The study has shown the sensitivity (91%) and specificity (87%) of the 5-word test in identifying patients with AD. CONCLUSION: This is a rapid (2 minutes) and simple test that is easy to use in medical practice for the screening of AD.

Age Factors↗
PubMed2002

Gelatinase B, PECAM-1 and MCP-3 gene polymorphisms in Belgian multiple sclerosis.

Polymorphic microsatellite markers in the genes for gelatinase B, PECAM-1 and MCP-3 have previously been analysed in Swedish and Sardinian individuals to test for association with multiple sclerosis (MS). Confirmation and comparison of genetic associations in various ethnic populations is mandatory and, therefore, we studied these three gene polymorphisms in 216 clinically definite MS patients and 193 normal controls, and in 148 simplex MS families, all of Belgian origin. No allelic associations were found between MS and the CA microsatellite marker in the promoter region of the gelatinase B gene, and the polymorphic CA repeat in the sixth intron of PECAM1. However, the two most abundant alleles of the CA/GA microsatellite polymorphism in the promoter-enhancer region of the MCP-3 gene, A2 (109 bp) and A3 (111 bp), were found to be significantly associated with disease in the case-control study [OR (95% CI)=0.68 (0.51-0.92), p (1 df)=0.015 and OR (95% CI)=1.62 (1.22-2.14), p (1 df)=0.0010, respectively], but not in the family study. These results are in agreement with previous findings in the Swedish and Sardinian populations and reinforce the possibility of a role for chemokines in MS pathogenesis.

Adult↗
PubMed2002

The neural system that bridges reward and cognition in humans: an fMRI study.

We test the hypothesis that motivational and cognitive processes are linked by a specific neural system to reach maximal efficiency. We studied six normal subjects performing a working memory paradigm (n-back tasks) associated with different levels of monetary reward during an fMRI session. The study showed specific brain activation in relation with changes in both the cognitive loading and the reward associated with task performance. First, the working memory tasks activated a network including the dorsolateral prefrontal cortex [Brodmann area (BA) 9/46] and, in addition, in the lateral frontopolar areas (BA 10), but only in the more demanding condition (3-back task). This result suggests that lateral prefrontal areas are organized in a caudo-rostral continuum in relation with the increase in executive requirement. Second, reward induces an increased activation in the areas already activated by working memory processing and in a supplementary region, the medial frontal pole (BA 10), regardless of the level of cognitive processing. It is postulated that the latter region plays a specific role in monitoring the reward value of ongoing cognitive processes. Third, we detected areas where the signal decreases (ventral-BA 11/47 and subgenual prefrontal cortices) in relation with both the increase of cognitive demand and the reward. The deactivation may represent an emotional gating aimed at inhibiting adverse emotional signals to maximize the level of performance. Taken together, these results suggest a balance between increasing activity in cortical cognitive areas and decreasing activity in the limbic and paralimbic structures during ongoing higher cognitive processing.

Adolescent↗
PubMed2002

Forced collectionism after orbitofrontal damage.

A collector is a person who collects things on purpose, either as a hobby or business, or for personal satisfaction, e.g., stamp, coin, or art collector. In such instances, the act of collecting things represents voluntary, controlled, goal-directed, selective searching. Pathologic patterns of collecting have been observed following brain damage, particularly frontal lobe damage, ranging from a tendency to grasp (prehension behavior) to an irrepressible need to seize surrounding objects and store them (hoarding behavior). These adnormal behaviors express an excessive adherence to environmental stimuli but in no way express a planned process directed toward specific items. In this article, we describe an unusual pattern of pathologic collecting behavior due to frontal lobe damage: involuntary irrepressible collecting that is goal-directed and selective. The authors report a patient who collected specifically household electrical appliances following a bilateral damage of orbito- and polar-prefrontal cortex. The patient had involuntary irrepressible collecting that was goal-directed and selective. This "forced collectionism" is different from that of the usual collectionism encountered in patients with frontal lobe lesions, as the latter is in no way a planned process directed toward specific items.

Adult↗
PubMed2002

Motivation, reward, and Parkinson's disease: influence of dopatherapy.

"Orbitofrontal" and "cingulate" striatofrontal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in motivation and sensitivity to reinforcement in animals. Parkinson's disease (PD) provides a model to assess their implications in humans. The aims of the study were to investigate motivation and sensitivity to reinforcement in non-demented and -depressed PD patients and to evaluate the influence of dopaminergic therapy by comparing patients in "on" (with L-Dopa) and "off" (without L-Dopa) states. Twenty-three PD patients were compared, in both the "on" and "off" states, to 28 controls, using: (1) an Apathy Scale; (2) Stimulus-Reward Learning, Reversal, and Extinction tasks; and (3) a Gambling task. PD patients were found: (1) mildly apathetic; (2) impaired on Stimulus-Reward Learning and Reversal, but not on Extinction; and (3) able to progress in the Gambling task during the first, but not the second assessment. There was no significant correlation between these various deficits. L-Dopa treatment clearly improved motivation, but had more limited and contrasting effects on other variables, decreasing the number of omission errors in Reversal, but increasing the number of perseveration errors in Extinction. These results suggest: (1) an implication of striatofrontal loops in human motivation and explicit and implicit sensitivity to reinforcement; (2) a positive influence of L-Dopa treatment on the subjective evaluation of motivation, but contrasting effects on reward sensitivity.

Adult↗
PubMed2002

[Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura].

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies (TMA). Both familial and sporadic forms exist: anaemia, thrombopaenia, renal failure and neurologic disorders are common clinical features. The differential diagnosis depends on plasma levels of von Willebrand factor-cleaving protease: there is a deficiency of this protease in patients with TTP whereas its rate is normal in HUS. We remind pathophysiology, etiologies and treatment of these TMA.

ADAM Proteins↗