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991.
Lonser RR Walbridge S Murray GJ Aizenberg MR Vortmeyer AO Aerts JM Brady RO Oldfield EH 《Annals of neurology》2005,57(4):542-548
Systemic enzyme replacement for Gaucher's disease has not prevented premature death or severe morbidity in patients with a neuronopathic phenotype, because the enzyme does not cross the blood-brain barrier. We used convection-enhanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examined its safety and feasibility for neuronopathic Gaucher's disease. Rats underwent intrastriatal infusion and were observed and then sacrificed at 14 hours, 4 days, or 6 weeks. Primates underwent serial magnetic resonance imaging during enzyme perfusion of the right frontal lobe or brainstem, were observed and then sacrificed after infusion completion. Animals underwent histologic and enzymatic tissue analyses. Magnetic resonance imaging revealed perfusion of the primate right frontal lobe or pons with infusate. Enzyme activity was substantially and significantly (p < 0.05) increased in cortex and white matter of the infused frontal lobe and pons compared to control. Immunohistochemistry demonstrated intraneuronal glucocerebrosidase. There was no toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Patients with neuronopathic Gaucher's disease and similar central nervous system disorders may benefit from this treatment. 相似文献
992.
Capella-McDonnall ME 《International journal of geriatric psychiatry》2005,20(9):855-861
OBJECTIVES: The primary purposes of this study were to determine the effect of dual sensory loss (i.e. combined hearing and vision loss) on depressive symptoms, to determine whether dual sensory loss has an effect on depressive symptoms when controlling for common covariates of depression, and to determine whether persons with dual sensory loss were more likely than those with a single sensory loss to experience depressive symptoms. DESIGN: Secondary analyses of 2001 National Health Interview Survey data. PARTICIPANTS: Nine thousand eight hundred and thirty-two people aged 55 and older residing in the community in the US. MEASUREMENTS: Self-report answers to questions about hearing and vision status, depressive symptoms, health, education level, poverty, social activities, social support, and functional disability (ADL and IADL status). RESULTS: Dual sensory loss had a significant effect on depressive symptoms (OR: 3.2, 95% CI: 2.8-4.0), which was lowered but still significant after controlling for covariates of depression (OR: 2.2, 95% CI: 1.7-2.9). Those with dual sensory loss were not significantly more likely than those with vision loss, but were significantly more likely than those with hearing loss, to experience symptoms of depression. CONCLUSION: Experiencing depressive symptoms is a problem that needs to be addressed with elderly persons with dual sensory loss. Not only is this population more likely to experience these symptoms, because of their sensory losses treatment for them may be problematical. Professionals working with the elderly should be aware of the increased risks of depressive symptoms in those with single or dual sensory loss, and should screen for them. If present, rehabilitation for sensory losses may help decrease them. 相似文献
993.
The factor structure and convergent and discriminant validity of the Anxiety Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans. Results from a confirmatory factor analysis (CFA) comparing our data to factor solutions commonly reported as representative of European American and Spanish populations indicated a poor fit. A subsequent exploratory factor analysis (EFA) indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2, Emotional Concerns) provided the best fit. Correlations between the ASI and anxiety measures were moderately high providing evidence of convergent validity, while correlations between the ASI and BDI were significantly lower providing evidence of discriminant validity. Scores on all measures were positively correlated with acculturation, suggesting that those who ascribe to more traditional Hispanic culture report elevated anxiety. 相似文献
994.
Bertocci MA Dahl RE Williamson DE Iosif AM Birmaher B Axelson D Ryan ND 《Journal of the American Academy of Child and Adolescent Psychiatry》2005,44(11):1158-1166
OBJECTIVE: Children with major depressive disorder (MDD) often complain of sleep disturbances; however, polysomnographic studies have failed to find objective evidence of these disturbances. This article examines subjective sleep reports of children with MDD and healthy controls focusing on comparing subjective and objective sleep measures. METHOD: Fifty-one subjects with MDD and 42 healthy subjects, 8-17 years old, participated in a comprehensive psychobiologic study including three nights of EEG sleep recording. Each morning, subjects completed a post-sleep form subjectively rating their sleep, which was then compared with their polysomnographic studies. RESULTS: Depressed subjects reported significantly worse sleep on four scales: subjective sleep quality, perceived number of awakenings, estimated minutes awake, and perceived ease of waking. In contrast to these subjective complaints, objective EEG measures indicated no evidence of disturbed sleep in the depressed sample compared to controls. Furthermore, exploratory analyses focusing on the subset of depressed subjects with the greatest subjective sleep disturbance showed, paradoxically, significantly better sleep in terms of the number of EEG awakenings and objective disturbances. CONCLUSIONS: Despite clinical evidence of subjective sleep complaints in depressed children, our EEG measures showed little evidence to indicate an objective basis for these perceptions. These findings raise provocative questions regarding the nature of sleep complaints associated with early-onset depression. 相似文献
995.
Taylor BA Hoch H Potter B Rodriguez A Spinnato D Kalaigian M 《Research in developmental disabilities》2005,26(4):385-392
This study examined the effects of manipulating establishing operations on the frequency of initiations of three children with autism toward peers with autism. The EO targeted was deprivation of preferred edibles, and the target initiation was a mand for the preferred snack. A reversal design was used to assess the effects of the EO conditions on frequency of initiations. Results indicated that when the EO was absent, no spontaneous initiations toward the peer occurred. Two participants required training sessions with an adult to transfer initiations toward peers. Once the EO had been established and was present, the participants initiated mands for the snack. Results are discussed in terms of implications for the use of establishing operations in language training for children with autism. 相似文献
996.
Ruggeri M Koeter M Schene A Bonetto C Vàzquez-Barquero JL Becker T Knapp M Knudsen HC Tansella M Thornicroft G;EPSILON Study Group 《Schizophrenia Research》2005,75(1):107-117
RATIONALE: The expanded version of the Brief Psychiatric Rating Scale (BPRS-E) has improved the instrument's coverage and interrater reliability, but there is little knowledge on its subsyndromes. OBJECTIVES: To assess: (1) whether there are common underlying BPRS-E subscales in patients living in different countries and (2) if this is the case, whether these subscales behave the same in all populations and, if not, what are the differences over these populations. METHODS: Data are part of the EPSILON study, a collaborative project carried out in Denmark, England, Holland, Italy and Spain. A random representative sample of 404 adult patients with a ICD-10 diagnosis of schizophrenia who have been in contact with mental health services of a defined catchment area in each site were assessed. Simultaneous component analysis (SCA) was used to find component weights that optimally explain the variance of the variables in different populations simultaneously. RESULTS: Symptom severity differed significantly among the five EPSILON sites in 12 out of 24 BPRS-E items, but a common component solution could be found. It explained 48.8% of the variance and gave four well-interpretable components: manic excitement/disorganization, depression/anxiety, negative and positive symptoms. Each component's internal consistency and intercomponent correlation matrix differed significantly among sites. The four components mean score differed significantly among sites for negative symptoms and depression/anxiety. CONCLUSIONS: In spite of the heterogeneity of symptom's severity in the various countries, the way symptoms cluster in schizophrenia is rather stable cross-culturally. Data demonstrate that to explore schizophrenia a third component, including mania/disorganization items, is necessary beside the positive-negative symptom dimensions. The subscales derived from these analyses can be readily used in clinical trials and epidemiological studies. 相似文献
997.
PURPOSE: The aim of this study was to examine the relationship between focal epileptic seizures and sleep through analysis of the cyclic alternating pattern (CAP). METHODS: We analyzed the recordings of a total of 56 nocturnal partial seizures (13 occurring as isolated events and 43 "in clusters" during a full-night ambulatory polysomnography) in 12 adult patients affected by localization-related focal epilepsy (7 males, 5 females; mean age 35+12.8 years; range 25-71). RESULTS: On exact binomial distribution analysis, seizures were more frequent in CAP than in non-CAP sleep, and in CAP phase A than in CAP phase B (p<0.001). Seizures occurring in clusters were more frequently associated with CAP sleep (p<0.05) than isolated seizures and first seizures of seizure clusters. Increase of CAP rate during the 30-min of sleep period after the occurrence of a seizure was documented in both cluster and isolated seizures. CONCLUSIONS: Our data indicate that an intra-sleep condition of highly fluctuating vigilance constitutes the real substrate for the occurrence of epileptic seizures regardless of the NREM stage in which they occur. The occurrence of partial seizures during sleep appears to induce sleep instability, which may in turn result in the facilitation of clusters of seizures. Together, these data highlight the potential of sleep fragmentation to modulate intra-sleep seizure occurrence. 相似文献
998.
999.
Human epidermis consists of a stratified epithelium mainly composed of keratinocytes and relies on a stem cell compartment to undergo constant regeneration. Genetic mutations affecting the capacity of basal keratinocytes to adhere firmly to the epidermal basement membrane lead to severe, and very often lethal, blistering disorders known as epidermolysis bullosa. Gene therapy represents a promising potential treatment for these devastating inherited disorders. Human epidermal stem cells can be cultivated ex vivo and stably transduced with integrating gene transfer vectors, allowing genetic and, more important, phenotypic correction of the adhesion properties of keratinocytes. Here we will review some of the issues that need to be addressed to make gene therapy a realistic treatment for these disorders, such as (1) which cells should be targeted, (2) which approach (in vivo or ex vivo) should be chosen, and (3) which gene transfer vector (retrovirus, lentivirus, or integrating nonviral strategies) should be used for stable gene correction. In the last 10 years, many reports have shown that gene transfer approaches to target epidermal stem cells are feasible and able to restore the adhesion properties of primary keratinocytes from patients with epidermolysis bullosa. In addition, tremendous progress has been achieved in culturing epidermal stem cells and generating sheets of stratified epithelium for permanent coverage of full-thickness burns. Gene modification of stem cells in combination with advanced tissue-engineering techniques could therefore represent a realistic option for patients with epidermolysis bullosa. 相似文献
1000.
Xu F Schaefer M Kida I Schafer J Liu N Rothman DL Hyder F Restrepo D Shepherd GM 《The Journal of comparative neurology》2005,489(4):491-500
It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high-resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2-Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed. 相似文献