128 research outputs found

    G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

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    Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

    Diagnostic reliability of magnetic resonance imaging for central nervous system syndromes in systemic lupus erythematosus: a prospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Previous studies of magnetic resonance imaging (MRI) as a diagnostic tool for central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) contained several limitations such as study design, number of enrolled patients, and definition of CNS syndromes. We overcame these problems and statistically evaluated the diagnostic values of abnormal MRI signals and their chronological changes in CNS syndromes of SLE.</p> <p>Methods</p> <p>We prospectively studied 191 patients with SLE, comparing those with (n = 57) and without (n = 134) CNS syndrome. CNS syndromes were characterized using the American College of Rheumatology case definitions.</p> <p>Results</p> <p>Any abnormal MRI signals were more frequently observed in subjects in the CNS group (n = 25) than in the non-CNS group (n = 32) [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7; <it>p </it>= 0.016] and the positive and negative predictive values for the diagnosis of CNS syndrome were 42% and 76%, respectively. Large abnormal MRI signals (ø ≥ 10 mm) were seen only in the CNS group (n = 7; RR, 3.7; CI, 2.9-4.7; <it>p </it>= 0.0002), whereas small abnormal MRI signals (ø < 10 mm) were seen in both groups with no statistical difference. Large signals always paralleled clinical outcome (<it>p </it>= 0.029), whereas small signals did not (<it>p </it>= 1.000).</p> <p>Conclusions</p> <p>Abnormal MRI signals, which showed statistical associations with CNS syndrome, had insufficient diagnostic values. A large MRI signal was, however, useful as a diagnostic and surrogate marker for CNS syndrome of SLE, although it was less common.</p

    Measuring Clients’ Perception of Functional Limitations Using the Perceived Functioning & Health Questionnaire

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    Background The Perceived Functioning & Health (PFH) questionnaire was developed to collect, in a standardized manner, which work activities are limited due to health conditions according to the perception of the client. In this study the questionnaire’s reliability and validity are investigated. Methods The PFH questionnaire is comprised of 147 questions, distributed over 33 scales, pertaining to the client’s psychosocial and physical work limitations. The PFH data of 800 respondents were analyzed: 254 healthy employees, 408 workers on sick leave and 138 recipients of a disability pension. Internal consistency (Cronbach’s α) for the scales was established. The test–retest reliability was examined for the data of 52 recipients of a disability pension who filled out the PFH twice within an interval of 1 month. Validation was established by taking the nature of the limitations as a criterion: mental limitations, physical limitations or a mix of both. To this end, the respondents were divided into groups distinguished on the basis of self-classification, as well as classification on the basis of disease codes given by insurance and occupational health physicians: a “healthy” group, subjects with only physical (“physical” group) or mental limitations (“mental” group) or mixed limitations (“mixed” group). The scale scores of these groups were compared and tested using analyses-of-variance and discriminant analyses. Results The scales were found to have sufficient to good internal consistency (mean Cronbach’s-α = 0.79) and test–retest reliability (mean correlation r = 0.76). Analyses-of-variance demonstrated significant differences between the scores of the mental, physical and healthy groups on most of the expected scales. These results were found both in groups defined by self-classification as well as in groups based on disease codes. Moreover, discriminant analyses revealed that the a priori classification of the respondents into three groups (mental, physical, healthy) for more than 75% of them corresponded with the classification on the basis of scale scores obtained from the questionnaire. Furthermore, limitations due to specific types of complaints (low back pain, fatigue, concentration problems) or diagnosed disorders (musculoskeletal disorders, reactive disorders, endogenous disorders) were clearly reflected in the scores of the related scales of the PFH. Conclusion The psychometric properties of the PFH with respect to reliability and validity were satisfactory. The PFH would appear to be an appropriate instrument for systematically measuring functional limitations in subjects on sick leave and in those receiving disability pensions, and could be used as a starting point in a disability claim procedure

    Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

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    BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient

    Protocol for Project FACT: a randomised controlled trial on the effect of a walking program and vitamin B supplementation on the rate of cognitive decline and psychosocial wellbeing in older adults with mild cognitive impairment [ISRCTN19227688]

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    BACKGROUND: the prevalence of individuals with cognitive decline is increasing since the number of elderly adults is growing considerably. The literature provides promising results on the beneficial effect of exercise and vitamin supplementation on cognitive function both in cognitively healthy as well as in the demented elderly. METHODS/DESIGN: the design is a two-by-two factorial randomised controlled trial. The study population consists of independently living elderly, between 70 and 80 years old, with mild cognitive impairment (MCI). In the RCT the effect of two interventions, a walking program and vitamin supplementation, is examined. The walking program (WP) is a group-based program aimed at improving cardiovascular endurance; frequency two lessons a week; lesson duration one hour; program duration one year. Non-walking groups receive a placebo activity program (PAP) (i.e. low intensive non-aerobic group exercises, like stretching) with the same frequency, lesson and program duration. Vitamin supplementation consists of a single daily vitamin supplement containing 50 mg B6, 5 mg folic acid and 0,4 mg B12 for one year. Subjects not receiving vitamin supplements are daily taking an identically looking placebo pill, also for a year. Participants are randomised to four groups 1) WP and vitamin supplements; 2) WP and placebo supplements; 3) PAP and vitamin supplements; 4) PAP and placebo supplements. Primary outcome measures are measures of cognitive function. Secondary outcomes include psychosocial wellbeing, physical activity, cardiovascular endurance and blood vitamin levels. DISCUSSION: no large intervention study has been conducted yet on the effect of physical activity and vitamin supplementation in a population-based sample of adults with MCI. The objective of the present article is to describe the design of a randomised controlled trial examining the effect of a walking program and vitamin B supplementation on the rate of cognitive decline in older adults with MCI

    Inhibition, Reinforcement Sensitivity and Temporal Information Processing in ADHD and ADHD+ODD: Evidence of a Separate Entity?

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    This study compared children with ADHD-only, ADHD+ODD and normal controls (age 8–12) on three key neurocognitive functions: response inhibition, reinforcement sensitivity, and temporal information processing. The goal was twofold: (a) to investigate neurocognitive impairments in children with ADHD-only and children with ADHD+ODD, and (b) to test whether ADHD+ODD is a more severe from of ADHD in terms of neurocognitive performance. In Experiment 1, inhibition abilities were measured using the Stop Task. In Experiment 2, reinforcement sensitivity and temporal information processing abilities were measured using a Timing Task with both a reward and penalty condition. Compared to controls, children with ADHD-only demonstrated impaired inhibitory control, showed more time underestimations, and showed performance deterioration in the face of reward and penalty. Children with ADHD+ODD performed in-between children with ADHD-only and controls in terms of inhibitory controls and the tendency to underestimate time, but were more impaired than controls and children with ADHD-only in terms of timing variability. In the face of reward and penalty children with ADHD+ODD improved their performance compared to a neutral condition, in contrast to children with ADHD-only. In the face of reward, the performance improvement in the ADHD+ODD group was disproportionally larger than that of controls. Taken together the findings suggest that, in terms of neurocognitive functioning, comorbid ADHD+ODD is a substantial different entity than ADHD-only
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