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PubMedDate not supplied

Excellent results with clorazepate in recalcitrant childhood epilepsies.

Eleven children with severe incapacitating generalized seizures were treated with sodium valproate and clorazepate and responded with a marked decrease in seizure frequency. Three children received clorazepate alone, either because of valproate toxicity or because of parental concern over side effects. These children, 5 males and 6 females, ranged in age from 3 to 17 years. They manifested normal to severely retarded intelligence. Although valproate levels were in the therapeutic range, seizure control was inadequate. When clorazepate was added to valproate therapy a marked reduction in seizure frequency occurred within 24 hours and became optimal within 48 to 72 hours. Side effects were minimal with the exception of a nocturnal generalized tonic-clonic seizure in a single patient. Three children were withdrawn from therapy after a year because of recurrent seizures. One patient was restarted on therapy after 6 months and seizure control improved. Clorazepate may be a useful adjunct in the treatment of primary generalized seizures in children.

Adolescent↗

PubMed2003

The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia.

Melperone, a butyrophenone, has been shown to possess atypical antipsychotic properties, i.e. ability to produce an antipsychotic effect in man at doses that cause minimal extrapyramidal side effects. In addition, melperone shares the following with other atypical antipsychotic drugs: (1) effectiveness for ameliorating negative symptoms; (2) no prolactin elevation; and (3) effectiveness in the treatment of some patients with neuroleptic-resistant schizophrenia. Other atypical antipsychotic drugs have been reported to improve cognitive function. This study was performed to investigate the effect of melperone on cognitive function. Nineteen patients with schizophrenia or schizoaffective disorder, including 11 neuroleptic-resistant patients, were treated with melperone for 6 weeks. A comprehensive neurocognitive test battery and psychopathological ratings (Brief Psychiatric Rating Scale, BPRS) were administered at baseline and after 6 weeks of melperone treatment. Treatment with melperone was associated with improvement in executive function, as measured by the Wisconsin Card Sorting Test (WCST)-Categories and WCST-Percent Perseveration. On the other hand, visuospatial manipulation, as measured by the Wechsler Intelligent Scale for Children-Revised (WISC-R) Maze, worsened during melperone treatment. There were no significant changes in other domains of cognition, i.e. verbal learning and memory, verbal working memory, verbal fluency and sustained attention. Scores of WCST-Categories and Perseveration at 6 weeks were predicted from the relevant cognitive test scores at baseline and the change in BPRS Total and Positive scores. These results suggest the usefulness of melperone for facilitating work and social function in patients with schizophrenia. The differences in the cognition-enhancing abilities between melperone and clozapine are discussed.

Analysis of Variance↗

PubMed1994

Effects of moclobemide on depressive symptoms and cognitive performance in a geriatric population: a controlled comparative study versus imipramine.

Moclobemide, a novel monoamine oxidase-A reversible inhibitor with demonstrated antidepressive efficacy, was administered double-blind versus imipramine to aged depressive subjects. The two drugs were given for 60 days in increasing doses up to 600 mg for moclobemide and 100 mg for imipramine. Fifteen patients received moclobemide and 15 received imipramine. Psychiatric conditions and symptoms were rated at 0, 7, 14, 30, 45, and 60 days after the beginning of the trial by means of the Scale for the Assessment of Psychoorganic Syndromes, Hamilton Rating Scale for Depression, Rome. Depression Inventory, Hamilton Anxiety Rating Scale, State-Trait Anxiety Inventory-X form, and the Clinical Global Impression Scale. Cognition was tested through the Benton visual retention test at days 0, 30, and 60 and the Digit Substitution Test of the Wechsler Adult Intelligence Scale at days 0 and 60. Side effects were assessed through the Dosage Record Emergent Symptoms at days 0, 7, 14, 30, 45, and 60. The dropout rate was significantly greater in the moclobemide group. Both drugs induced an improvement in depressive and anxious symptomatology, with moclobemide showing a faster onset. Furthermore, moclobemide showed an enhancing effect on cognition, which was not shown by imipramine. Such results indicate that moclobemide could prove to be the drug of choice in geriatric depression, given that cognitive effects are prominent in the aged.

Aged↗

PubMed1994

Electro-driven chemomechanical polymer gel as an intelligent soft material.

Weakly crosslinked poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel was synthesized and the chemomechanical behaviors in the presence of N-alkylpyridinium chloride (CnPyCl n = 4, 12, 16) were studied. The principle of this behavior is based upon an electrokinetic molecular assembly reaction of surfactant molecules on the polymer gel caused by both electrostatic and hydrophobic interactions. Under an electric field PAMPS gel underwent significant and quick bending and the response could be controlled effectively by changing the alkyl chain length of the surfactant molecule, the salt concentration, and the current applied. The results allow us to consider that cooperative complex formation between PAMPS gel and CnPyCl is responsible for this effective chemomechanical behavior.

Biocompatible Materials↗

PubMed2003

OQAFMA Querying agent for the Foundational Model of Anatomy: a prototype for providing flexible and efficient access to large semantic networks.

The development of large semantic networks, such as the UMLS, which are intended to support a variety of applications, requires a flexible and efficient query interface for the extraction of information. Using one of the source vocabularies of UMLS as a test bed, we have developed such a prototype query interface. We first identify common classes of queries needed by applications that access these semantic networks. Next, we survey StruQL, an existing query language that we adopted, which supports all of these classes of queries. We then describe the OQAFMA Querying Agent for the Foundational Model of Anatomy (OQAFMA), which provides an efficient implementation of a subset of StruQL by pre-computing a variety of indices. We describe how OQAFMA leverages database optimization by converting StruQL queries to SQL. We evaluate the flexibility and efficiency of our implementation using English queries written by anatomists. This evaluation verifies that OQAFMA provides flexible, efficient access to one such large semantic network, the Foundational Model of Anatomy, and suggests that OQAFMA could be an efficient query interface to other large biomedical knowledge bases, such as the Unified Medical Language System.

Abstracting and Indexing↗

PubMed2006

Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review.

BACKGROUND: More and more epidemiological, genetic and neuroimaging studies show similarities between bipolar disorder (BD) and schizophrenia (SZ). Cognitive functions are known to be highly impaired in SZ and are increasingly studied in BD. When both populations are compared, the conclusions appear to be contradictory. The purpose of this review is to help define the profile of cognitive deficits in BD and in SZ. METHODS: A systematic review of the literature of neuropsychological studies comparing BD and SZ was made, beginning in January 1990 and ending in January 2005. Thirty-eight studies met the required quality criteria and were included in this review. RESULTS: Bipolar patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. However, when compared to schizophrenic patients, bipolar patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory and executive functions. When looking into effect sizes, there seem to be different profiles even in studies finding no significant differences. CONCLUSIONS: The neuropsychological differences reported between both groups could be due to the presence of psychotic features, to environmental factors (stressful events, duration of the disease and number of hospitalisations) and could also be related to differences during the neurodevelopmental phase. Further studies should confirm whether these results are truly related to different neurobiological backgrounds.

Antipsychotic Agents↗

PubMed2003

Will the digital computer transform classical mathematics?

Mathematics and machines have influenced each other for millennia. The advent of the digital computer introduced a powerfully new element that promises to transform the relation between them. This paper outlines the thesis that the effect of the digital computer on mathematics, already widespread, is likely to be radical and far-reaching. To articulate this claim, an abstract model of doing mathematics is introduced based on a triad of actors of which one, the 'agent', corresponds to the function performed by the computer. The model is used to frame two sorts of transformation. The first is pragmatic and involves the alterations and progressive colonization of the content and methods of enquiry of various mathematical fields brought about by digital methods. The second is conceptual and concerns a fundamental antagonism between the infinity enshrined in classical mathematics and physics (continuity, real numbers, asymptotic definitions) and the inherently real and material limit of processes associated with digital computation. An example which lies in the intersection of classical mathematics and computer science, the P=NP problem, is analysed in the light of this latter issue.

Artificial Intelligence↗

PubMed1991

Substance abuse and schizophrenia: effect on symptoms but not on neurocognitive function.

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.

Adult↗

PubMed2003

Intellectual freedom and editorial responsibilities within the context of controversial research.

The primary purpose of this article is to explore the limits that an agent, such as the government or the American Psychological Association, may place on one's right to pursue a program of research or to share the findings of a research project. The primary argument that evolves here is that researchers' rights to pursue an interesting hypothesis, and their freedom of expression, are conditional. The author examines the potential pragmatic and epistemological barriers to a program of research and the responsibilities that researchers bear to address epistemological and nonepistemological matters while reviewing the implications of their work.

Behavioral Research↗

PubMed2006

Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.

OBJECTIVE: Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy. METHODS: The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of alpha-dystroglycan in skeletal muscle. RESULTS: We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness. INTERPRETATION: Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L.

Anti-Inflammatory Agents↗

PubMed2005

Robust quantification of in vitro angiogenesis through image analysis.

An automated image analysis method for quantification of in vitro angiogenesis is presented. The method is designed for in vitro angiogenesis assays that are based on co-culturing endothelial cells with fibroblasts. Such assays are used in many current studies in which anti-angiogenic agents for the treatment of cancer are being sought. This search requires accurate quantification of the stimulatory and inhibitory effects of the different agents. The quantification method gives lengths and sizes of the tubule complexes as well as the numbers of junctions in each of them. The method is tested with a set of test images obtained with a commercially available in vitro angiogenesis assay. The results correctly indicate the inhibitory effect of suramin and the stimulatory effect of vascular endothelial growth factor. Moreover, the image analysis method is shown to be robust against variations in illumination. We have implemented a software package that utilizes the methods. The software as well as a set of test images are available at http://www.cs.tut.fi/sgn/csb/angioquant/.

Algorithms↗

PubMed2003

High-dimensional analysis of evolutionary autonomous agents.

This article presents a new approach to the important challenge of localizing function in a neurocontroller. The approach is based on the basic functional contribution analysis (FCA) presented earlier, which assigns contribution values to the elements of the network, such that the ability to predict the network's performance in response to multi-unit lesions is maximized. These contribution values quantify the importance of each element to the tasks the agent performs. Here we present a generalization of the basic FCA to high-dimensional analysis, using high-order compound elements. Such elements are composed of conjunctions of simple elements. Their usage enables the explicit expression of sets of neurons or synapses whose contributions are interdependent, a prerequisite for localizing the function of complex neurocontrollers. High-dimensional FCA is shown to significantly improve on the accuracy of the basic analysis, to provide new insights concerning the main subsets of simple elements in the network that interact in a complex nonlinear manner, and to systematically reveal the types of interactions that characterize the evolved neurocontroller.

Artificial Intelligence↗

PubMed2004

Association of anticholinergic load with impairment of complex attention and memory in schizophrenia.

OBJECTIVE: The authors' goals were 1) to establish a clinically useful standard index of the relative anticholinergic potency of psychiatric medications; 2) to determine which cognitive functions are most affected by the administration of anticholinergic medications to patients with schizophrenia; and 3) to compare in vitro and clinically derived indexes of anticholinergic load in predicting these cognitive impairments. METHOD: One hundred six clinically stable patients with schizophrenia were given a brief neuropsychological battery and evaluated on a standard symptom rating scale. The anticholinergic load associated with their psychiatric medications was estimated by using 1) a pharmacological index, calculated from a compilation of published studies reporting in vitro brain muscarinic receptor antagonism, and 2) a clinical index, based on clinician ratings of the anticholinergic side effects of medications. The authors analyzed the correlations of both indexes with the neuropsychological measures and with summary neuropsychological factor scores. RESULTS: The clinical and pharmacological anticholinergic indexes were highly correlated with each other and showed virtually identical associations with neuropsychological measures. Anticholinergic load was associated with lower scores on measures of attention and declarative memory, including several measures of auditory and visual memory and two tests of complex attention, but was unrelated to intelligence, simple attention, working memory, executive functions, conceptual fluency, or motor speed. CONCLUSIONS: This pattern of cognitive impairment with central cholinergic antagonism is consistent with emerging models of the functional anatomy of ascending forebrain cholinergic subsystems. Both pharmacological and clinical indexes show utility in predicting the effects of anticholinergic load on cognition in schizophrenia. Doses of psychiatric medication within the range of routine pharmacotherapy practice may have clinically significant effects on memory and complex attention in patients with schizophrenia; these effects may contribute as much as one-third to two-thirds of the memory deficit typically seen in patients with schizophrenia.

Adult↗

PubMed2006

Review of antipsychotics in children and adolescents.

The use of antipsychotics in children and adolescents in the clinical setting is increasing. This article reviews 77 clinical trials published in the last 10 years, investigating their efficacy, effectiveness, safety and pharmacokinetic data in paediatric populations. The diagnostic categories in which the antipsychotics are commonly used (schizophrenia, pervasive developmental disorders, Tourette's disorder, mental retardation/subaverage intelligence, mood disorders and disruptive behaviour disorders) were used in order to review the evidence and effectiveness. All randomised, double-blind, placebo-controlled trials from the past decade are also summarised. This review refers to recent relevant practice parameters, guidelines and reviews throughout the text. Consistent with previous reviews, it is concluded that the recent trend of increased use of antipsychotics in children and adolescents is not adequately supported by evidence. Specific suggestions have been provided on how to incorporate the existing evidence base into clinical decision making. The review ends with the authors' opinion on the clinical and research implications for the field and future directions.

Adolescent↗

PubMed2000

Effects of central dopaminergic stimulation by apomorphine on speech in Parkinson's disease.

OBJECTIVE: To determine the effect of central dopaminergic stimulation with apomorphine on speech in PD. BACKGROUND: Most patients with PD have a speech disorder. Of those, 89% have involvement of laryngeal function, and 45% have additional articulatory dysfunction. The effect of dopaminergic medications on these two dimensions of speech impairment in PD has not been selectively studied. METHODS: In a randomized, double-blind, placebo-controlled crossover design, patients with PD and speech impairment, Hoehn and Yahr stages 2 to 4 "off," and without severe dyskinesias were given placebo or apomorphine injections 0.05 mg/kg subcutaneously during two consecutive outpatient visits. They were pretreated with domperidone for 48 hours and were tested off their parkinsonian medications for 12 hours. Laryngeal function was assessed by maximum sustained vowel phonations and comfortable vowel phonations. Articulatory function was evaluated by speech intelligibility score, speaking rate, and efficiency ratio. RESULTS: Ten patients, mean age 73.4 years (SD = 6.6), disease duration 8.7 years (SD = 6.3), were tested. The baseline motor score on the Unified Parkinson's Disease Rating Scale (UPDRSm) and all experimental speech variables were equivalent on both placebo and apomorphine days. At a dose of apomorphine that provoked improvement in UPDRSm (p = 0.0078), no index of either laryngeal or articulatory function improved significantly after apomorphine administration. CONCLUSION: Laryngeal and articulatory speech components are not under prominent dopaminergic control in PD. Treatment regimens should focus on nondopaminergic pharmacology and other therapies.

Aged↗

PubMedDate not supplied

[Effect of olanzapine treatment on cognitive functions in patients with schizophrenia].

AIM: The aim of this study was to assess whether olanzapine treatment results in an improvement of cognitive functions that became impaired by the schizophrenic process. METHOD: The correlation of the intensity of schizophrenic symptoms and duration of the disease with the level of cognitive functions were also examined. The schizophrenic patients were examined in three steps: before beginning of olanzapine treatment, after 6 weeks of treatment, and after approximately 12 months since the beginning of the olanzapine treatment, 36 patients were examined (9 female, 27 male) aged 20-53 (X = 25.4). The following tests were applied: Positive and Negative Syndromes Scale--PANSS, Squire's Memory Questionnaire, sub-scales: Digit span and Similarities of the Wechsler's Intelligence Scale, Long-term memory sub-test of the Choynowski's Memory Scale, Diagnosis of Brain Damages, Clock Completion Test, Decroly's Box. RESULTS: The olanzapine treatment of schizophrenia was characterised by significant antipsychotic efficacy including both positive and negative symptoms. The positive symptoms were associated with the attention range, the planning process context and the immediate memory with the tendency towards loosing remembrance in the process of non-verbal learning. The negative symptoms were associated with concrete conceptual thinking. Improvement of cognitive functions was noted for almost all of the examined functions. The effect of olanzapine therapy in schizophrenic patients may be regarded as personality integrating.

Adult↗

PubMed2006

Nanotechnology: intelligent design to treat complex disease.

The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

Animals↗

PubMed2026

Recent advances for the pharmaceutical production of highly attenuated poxviruses as viral vector platforms.

INTRODUCTION: Highly attenuated poxviruses serve as potent viral vectors, oncolytic agents, and therapeutic vaccines. They can accommodate and stably maintain a large genomic payload of foreign inserts. Their limited replication in human cells provides an excellent safety profile, but it concomitantly necessitates higher doses of infectious particles for full therapeutic efficacy. AREAS COVERED: We review recent advances in bioprocesses for the pharmaceutical production of poxvirus-based vectors, focusing mainly on the vaccinia virus and the Orf virus. These include upstream processing using highly permissive cell substrates, optimized feeding strategies, and a virus phenotype that facilitates downstream processing. The study explores ongoing challenges and identifies strategies to adapt the downstream process to intensified upstream processes in order to achieve an economic end-to-end production. EXPERT OPINION: For notably increased virus yields of up to 2 log after amplification, we propose to replace classic adsorption chromatography by a collective and continuous purification platform for separating the virus from process-related impurities. Filtration operations facilitate process scalability while reducing volumes, which is beneficial for a flow-through polishing to meet pharmaceutical quality attributes. Combined with artificial intelligence modeling, these advancements alleviate financial pressures on healthcare systems and accelerate the production of novel vaccine candidates for clinical use.

Humans↗