Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats.
1. We have previously demonstrated that continuous i.c.v. infusion of amyloid beta-peptide (A beta), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2. In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A beta-(1-42)-induced learning and memory deficits in rats. 3. In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A beta-(40-1)-infused control rats. 4. Nefiracetam, at a dose range of 1-10 mg kg(-1), improved learning and memory deficits in the A beta-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats. 6. Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A beta-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease. (+info)
The generalised form of epimerase deficiency galactosaemia has been described in only two children from unrelated families. Their progress is reported and three other affected children from these families are described. The initial presentation was similar to classic galactosaemia. Despite treatment all have shown poor growth and moderate learning difficulties. Three have sensorineural deafness and four have pronounced dysmorphic features. The two older female patients have normal pubertal development. (+info)
Assessing general practitioners' care of adult patients with learning disability: case-control study.
OBJECTIVE: To compare general practitioners' care of adult patients with learning disability with that of control patients in the same practice. DESIGN: Case-control study of patients and controls by a structured interview study of general practitioners. SETTING: Avon. PATIENTS: 78 adult patients with learning disability and 78 age and sex matched controls--cared for by 62 general practitioners. MAIN MEASURES: Number and content of consultations and opinions of the general practitioners. RESULTS: There were more consultations for diseases of the central nervous system and of the skin among the patients than the controls (15 v 3 for central nervous system disease and 15 v 4 skin disease). There were also significantly fewer recordings of blood pressure and cervical cytology tests (34 v 51 for blood pressure and 2 v 18 for cytology). Although more patients were taking drugs affecting the central nervous system (33 v 6), more controls were taking drugs for musculoskeletal complaints (17 v 7). CONCLUSION: Although adult patients with learning disability consult with their general practitioners at equivalent rates to other patients, they get less preventive care and consult for different types of problems than do other patients. The reasons for these differences in preventive care are not clear. Carers and general practitioners should be informed of these differences to ensure that appropriate care is given. (+info)
Cognitive functioning in people with epilepsy plus severe learning disabilities: a systematic analysis of predictors of daytime arousal and attention.
In spite of the high prevalence of epilepsy and the importance of preserving cognitive function in people with learning disabilities, this population has received relatively little research attention. This study sets out systematically to investigate possible predictive factors of inter-ictal states of arousal and attention. The daytime function of 28 people with epilepsy and severe learning disabilities was assessed by performance on a two-choice reaction time vigilance task, behavioural analysis of time-sampled video recordings taken in naturalistic settings, and carer ratings on visual analogue scales. This methodology yielded eight discrete functional measures, from which two further index measures were derived after principal components analysis. A range of clinical and psychosocial assessments was completed and subjects had 36 hour ambulatory EEG and sleep EEG monitoring. Regression models identified significant predictors of cognitive function from a range of potential explanatory variables i.e. demographic, clinical, pharmacological, background EEG rhythms and sleep parameters. Results indicated that greater severity of learning disability, longer bedtime periods, poor sleep efficiency, frequent seizures and antiepileptic drug polytherapy were significant predictor variables. Explained variance (adjusted R2) was greater than 50% for six of 10 outcome variables (range up to 85%). Furthermore, significant regression equations (P < 0.05) were obtained for all but one variable. Thus, these results appear reasonably robust. Results support an interactional model of daytime arousal and attention in people with epilepsy plus severe learning disabilities. Inter-ictal cognitive function appears to be mediated by a combination of organic, circadian (sleep wake), clinical and pharmacological factors. (+info)
School problems and the family physician.
Children with school problems pose a challenge for the family physician. A multidisciplinary team of professionals can most appropriately assess and manage complex learning problems, which are often the cause of poor school performance. The family physician's primary role in this process is to identify or exclude medical causes of learning difficulties. An understanding of the complicated nature of school problems, the methods used to assess, diagnose and treat them, and the resources available to support the child and family are essential to successful management. Various references and resources are helpful for a more in-depth study of specific school problems. (+info)
The management of epilepsy in a hospital for people with a learning disability.
The study examined changes in the use of antiepileptic drugs (AEDs) in a large hospital for people with a learning disability over a 2 year period, the use of investigations, and the presence of medication side-effects. The surveys were carried out in 1993 and 1995/6. In 1993, 27% of patients were being treated for epilepsy and in 1995/6, 30.1%. Ninety percent and 82.4% of patients, respectively, were receiving one or two AEDs. In the second survey there were fewer prescriptions for phenobarbitone (5.8% vs. 12.5%) and an increase in the use of lamotrigine (21.6% vs. 5%), gabapentin (5.8% vs. 0) and vigabatrin (3.9% vs. 2.5% in 1993). Side-effects were recorded in 6 (11.8%) patients. Seven (21.2%) patients receiving carbamazepine were found to have hyponatraemia. Of the 54 electroencephalograms (EEGs) requested, 41 (76%) were reported as abnormal. Six CT brain scans had been conducted, of which five were abnormal. People receiving antipsychotic drugs had fewer seizures than average. (+info)
The attenuation of learning impairments induced after exposure to CO or trimethyltin in mice by sigma (sigma) receptor ligands involves both sigma1 and sigma2 sites.
1. Sigma (sigma) receptor ligands were previously reported to alleviate learning and memory impairments on several pharmacological and pathological rodent models of amnesia. Such effect was demonstrated as involving the sigma1 subtype of sigma receptor. 2. In this study, we characterized the pharmacological effect mediated by sigma ligands on two lesional models of amnesia in mice: (1) the hypoxia-related learning and memory impairment model induced by repeated exposure to carbon monoxide (CO) gas; and (2) the intoxication with trimethyltin (1 mg kg(-1)). 3. The selective sigma1 ligand PRE-084 (1 mg kg(-1)) or the non-selective sigma1/sigma2 compounds DTG (0.1 mg kg(-1)), BD1008 (3 mg kg(-1)), and haloperidol (0.1 mg kg(-1)) reversed significantly the spontaneous alternation deficits observed 7 days after exposure to CO or 14 days after intoxication with trimethyltin. 4. The selective sigma1 receptor antagonist NE-100 (1 mg kg(-1)) was ineffective by itself, but blocked completely the PRE-084 effects, partially the DTG effects, and did not affect the effects induced by BD1008 or haloperidol. 5. A similar pharmacological profile was observed in the step-down type passive avoidance test performed 8 days after exposure to CO. 6. These results show that, in contrast to the previously reported amnesia models, the impairments induced after exposure to CO or intoxication with trimethyltin could be alleviated not only by sigma1 receptor agonists but also by sigma2 agonists. The particular pattern of neurodegeneration observed in these lesional models may explain these differences. (+info)
Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome.
Human Sim2 is a product of one of the genes located on human chromosome 21q22 and is a homolog of Drosophila single-minded ( sim ) which is a critical player in midline development of the central nervous system of the fly. Since Sim2 mRNA is expressed in facial, skull, palate and vertebra primordia in human and rodent embryos, features that are associated with phenotypes of Down's syndrome (DS), its trisomic state is suspected to contribute to the symptoms of DS. Here we describe that mSim2 mRNA is expressed in hippocampus and amygdala of adult mice, and that while mice overexpressing mSim2 under the control of the beta-actin promoter are viable and fertile and have superficially normal skeletal, brain and heart structures, they exhibit a moderate defect in context-dependent fear conditioning and a mild defect in the Morris water maze test. Taken together, our data show that overdosage of Sim2 may be important for the pathogenesis of Down's syndrome, especially mental retardation. (+info)