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Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice

Jr., A. S. Aguiar; Moreira, E. L. G.; Hoeller, A. A.; Oliveira, P. A.; Córdova, F. M.; Glaser, V.; Walz, R.; Cunha, R. A.; Leal, R. B.; Latini, A.; Prediger, R. D. S.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
POR
Relevância na Pesquisa
37.2%
l-DOPA alleviates the motor symptoms of Parkinson’s disease, but its long-term use is associated with undesirable dyskinesia. We now tested whether exercise can attenuate this l-DOPA-induced dyskinesia (LID). We tested the effects of exercise on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. Animals were treated with l-DOPA/benserazide (25/12.5 mg/kg, i.p.) without and with possibility to exercise (running wheel) during 2 weeks. Exercise drastically prevented the development of LID, and its associated aberrant striatal signaling, namely the hyperphosphorylation of dopamine and cAMP-regulated phosphoprotein 32 kDa protein and c-Fos expression. Our results indicate that exercise can partially prevent the development of LID through the normalization of striatopallidal dopaminergic signaling.

Does the degree of smoking effect the severity of tardive dyskinesia? A longitudinal clinical trial

DIEHL, A.; REINHARD, I.; SCHMITT, A.; MANN, K.; GATTAZ, W. F.
Fonte: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER Publicador: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.05%
Background. - Tardive dyskinesia (TD) is a movement disorder observed after chronic neuroleptic treatment. Smoking is presumed to increase the prevalence of TD. The question of a cause-effect-relationship between smoking and TD, however, remains to be answered. Purpose of this study was to examine the correlation between the degree of smoking and the severity of TD with respect to differences caused by medication. Method. - We examined 60 patients suffering from schizophrenia and TD, We compared a clozapine-treated group With a group treated with typical neuroleptics. Movement disorders were assessed using the Abnormal-Involuntary-Movement-Scale and the technical device digital image processing, providing rater independent information on perioral movements. Results. - We found a strong correlation (.80 < r < .90, always p < .0001) between the degree of smoking and severity of TD. Repeated measurements revealed a positive correlation between changes in cigarette consumption and changes of the severity of TD (p < .0001). Analyses of covariance indicated a significant group-effect with a lower severity of TD in the clozapine-group compared to the typical-neuroleptics-group (p = .010). Interaction-analyses indicated a higher impact of smoking oil the severity of TD in the typical-neuroleptics-group compared to the clozapine-group (p = .033). Conclusion. - Concerning a possible cause-effect-relationship between smoking and TD...

A study on the action of two calcium channel blockers (verapamil and flunarizine) upon an experimental model of tardive dyskinesia in rats

Pereira,João S.; Bertolucci,Paulo H. P.; Ferraz,Henrique B.; Andrade,Luiz A. F. de
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/1992 EN
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37.05%
Tardive dyskinesia (TD), a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB) drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphyne was rated. The CCB drugs were administered in acute (in the 28th. day) and chronic (for 8 days, after the 25th day) experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD.

Dyskinesia induced by phenytoin

MONTENEGRO,M. AUGUSTA; SCOTONI,ANNA ELISA; CENDES,FERNANDO
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/1999 EN
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37.49%
Phenytoin is an effective antiepileptic drug, although, it can be associated with many side effects, including dyskinesia. OBJECTIVE: To describe the clinical characteristics of phenytoin induced dyskinesia. METHODS: We investigated the occurrence of involuntary movements in patients followed at our adult and pediatric epilepsy clinics during the period of one year. RESULTS: Three patients presented with phenytoin-induced dyskinesia: one adult with axial and orofacial dyskinesia, and two children with choreoathetosis. They did not have other signs of phenytoin intoxication and had complete recovery after phenytoin withdrawal. CONCLUSION: Phenytoin induced dyskinesia may occur during either chronic or initial treatment and with normal serum phenytoin levels. However, it occurs most often in patients on polytherapy, usually after increasing dosage and with toxic serum levels. Other signs of phenytoin intoxication may be present in these patients, but often the dyskinesia is the only side effect, which may delay the diagnosis and treatment. The clinical characteristics of the involuntary movements vary and may be focal or generalized, most often characterized by choreoathetosis and dyskinesias. These may last for hours, days or even years...

Reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS) for tardive dyskinesia in Brazilian patients

Tonelli,H.; Tonelli,D.; Poiani,G.R.; Vital,M.A.B.F.; Andreatini,R.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2003 EN
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37.05%
The objective of the present study was to evaluate the reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS). Videotaped interviews with 16 psychiatric inpatients treated with antipsychotic drugs for at least 5 years were evaluated. Reliability was assessed by the intraclass correlation coefficient (ICC) between three raters, two with and one without clinical training in psychopathology. Clinical utility was assessed by the difference between the scores of patients with (N = 11) and without (N = 5) tardive dyskinesia (TD). Patients with TD exhibited a higher severity of global evaluation by the AIMS (sum of scores: 4.2 ± 0.9 vs 0.4 ± 0.2; score on item 8: 2.3 ± 0.3 vs 0.4 ± 0.2, TD vs controls). The ICC for the global evaluation was fair between the two skilled raters (0.58-0.62) and poor between these raters and the rater without clinical experience (0.05-0.29). Thus, we concluded that the Portuguese version of the AIMS shows an acceptable inter-rater reliability, but only between clinically skilled raters, and that it is clinically useful.

An examination of synaptic proteins following chronic haloperidol in a rat model of tardive dyskinesia

Kessas,Mona; Creed,Meaghan; Nobrega,José N.
Fonte: Pontificia Universidade Católica do Rio de Janeiro; Universidade de Brasília; Universidade de São Paulo Publicador: Pontificia Universidade Católica do Rio de Janeiro; Universidade de Brasília; Universidade de São Paulo
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2010 EN
Relevância na Pesquisa
37.05%
Tardive dyskinesia (TD) is a late-onset side effect mainly affecting the orofacial region of patients treated chronically with classic antipsychotic drugs such as haloperidol (HAL). The causes of TD remain unknown. We hypothesized that faulty synaptic re-organization might be related to TD-like syndromes and used the vacuous chewing movements (VCM) model in rats to investigate the expression of four synaptic proteins, synaptophysin, syntaxin, spinophilin and PSD-95, in brains of HAL-treated rats. Male Sprague-Dawley rats were treated for 14 weeks with either haloperidol decanoate (21 mg/kg once every 3 weeks, I.M) or vehicle and VCMs were monitored on a weekly basis. As expected, VCMs developed reliably and were consistently more pronounced in some rats than in others. Using immunohistochemistry in anatomically preserved brain sections as well as Western Blot analyses of whole cells or synaptosomal fractions in striatal tissue, we found no significant effect of chronic HAL on levels of these proteins. Neither did we find significant differences in the levels of the four synaptic markers when comparing rats showing High vs. Low levels of VCMs. These results suggest that structural synaptic alterations (e.g. involving increased number of synapses) may not be the underlying mechanism of oral dyskinesias induced by chronic antipsychotic drug treatment. The possibility that functional neuroplastic changes occur remains to be investigated.

Priming for L-dopa-induced dyskinesia in Parkinson’s disease: a feature inherent to the treatment or the disease?

Nadjar, Agnès; Gerfen, Charles R.; Bezard, Erwan
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.49%
Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson’s disease ultimately experienced by the vast majority of patients. This article does not review the increased understanding of dyskinesia pathophysiology we have seen during the past few years but, instead, specifically focuses upon the very first molecular events thought to be responsible for the establishment of dyskinesia and generally grouped under the term of “priming”. Priming is classically defined as the process by which the brain becomes sensitized such that administration of a dopaminergic therapy modifies the response to subsequent dopaminergic treatments. In this way, over time, with repeated treatment, the chance of dopaminergic stimulation eliciting dyskinesia is increased and once dyskinesia has been established, the severity of dyskinesia increases. In this opinion review, however, we aim at strongly opposing the common view of priming. We propose, and hopefully will demonstrate, that priming does not exist per se but is the direct and intrinsic consequence of the loss of dopamine innervation of the striatum (and other target structures), meaning that the first injections of dopaminergic drugs only exacerbate those mechanisms (sensitization) but do not induce them. Chronicity and pulsatility of subsequent dopaminergic treatment only exacerbates the likelihood of developing dyskinesia.

Risperidone and Olanzapine Induced Tardive Dyskinesia : A Critical Review of Reported Cases

Singh, Gurvinder Pal
Fonte: Medknow Publications Publicador: Medknow Publications
Tipo: Artigo de Revista Científica
Publicado em //2004 EN
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27.56%
Risperidone and olanzapine in treatment of psychiatric patients can provoke a plethora of tardive dyskinesias which pose problems for them. This clinical problem requires the urgent attention of mental health professionals. Hence a comprehensive research of Medline and related literature was undertaken from 1996 till August 2004. The published twenty two cases of risperidone (N=12) or olanzapine (N=10) induced tardive dyskinesia were critically reviewed and an attempt is being made to clarify the various issues associated with them. In these reports majority of patients were in younger age group, females and the interval until onset of tardive dyskinesia after initiation of risperidone or olanzapine was within one year. In eight reported cases of risperidone induced and three cases of olanzapine induced tardive dyskinesia, TD disappears either by stopping the drug or switching to other atypical antipsychotic drug. In seven cases of risperidone induced and three cases of olanzapine induced tardive dyskinesia, there was previous exposure to conventional antipsychotic drugs. It is concluded that induction of tardive dyskinesia by these medications is insufficiently documented in these reports but in some cases evidence is suggestive of the role of these drugs in development of tardive dyskinesia. There is no generally accepted treatment for tardive dyskinesia...

The Emerging Genetics of Primary Ciliary Dyskinesia

Zariwala, Maimoona A.; Omran, Heymut; Ferkol, Thomas W.
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
37.05%
Primary ciliary dyskinesia (PCD) is an autosomal recessive, rare, genetically heterogeneous condition characterized by oto-sino-pulmonary disease together with situs abnormalities (Kartagener syndrome) owing to abnormal ciliary structure and function. Most patients are currently diagnosed with PCD based on the presence of defective ciliary ultrastructure. However, diagnosis often remains challenging due to variability in the clinical phenotype and ciliary ultrastructural changes. Some patients with PCD have normal ciliary ultrastructure, which further confounds the diagnosis. A genetic test for PCD exists but is of limited value because it investigates only a limited number of mutations in only two genes. The genetics of PCD is complicated owing to the complexity of axonemal structure that is highly conserved through evolution, which is comprised of multiple proteins. Identifying a PCD-causing gene is challenging due to locus and allelic heterogeneity. Despite genetic heterogeneity, multiple tools have been used, and there are 11 known PCD-causing genes. All of these genes combined explain approximately 50% of PCD cases; hence, more genes need to be identified. This review briefly describes the current knowledge regarding the genetics of PCD and focuses on the methodologies used to identify novel PCD-causing genes...

Update of Respiratory Tract Disease in Children with Primary Ciliary Dyskinesia

Sagel, Scott D.; Davis, Stephanie D.; Campisi, Paolo; Dell, Sharon D.
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
37.05%
Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by abnormal ciliary structure and function leading to impaired mucociliary clearance and chronic progressive sinopulmonary disease. Upper and lower respiratory tract manifestations are cardinal features of PCD. This review summarizes the current state of knowledge of respiratory tract disease in individuals with PCD and highlights the challenges in identifying and quantifying lung disease in very young children with PCD. No specific therapies are available to correct ciliary dysfunction in PCD. Treatment is not evidence based, and recommendations are largely extrapolated from cystic fibrosis and other conditions with impaired mucociliary clearance. There is a pressing need to develop and validate outcome measures, including patient-reported outcomes, that could be used to evaluate potential therapies in PCD. This review concludes with recommendations for clinical endpoints and outcome measures and a prioritized list of treatments to study in PCD clinical trials.

The prevalence of clinical features associated with primary ciliary dyskinesia in a heterotaxy population: results of a web-based survey

Shapiro, Adam J.; Tolleson-Rinehart, Sue; Zariwala, Maimoona A.; Knowles, Michael R.; Leigh, Margaret W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.62%
Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of primary ciliary dyskinesia patients, but the prevalence of primary ciliary dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in primary ciliary dyskinesia and that might suggest the possibility of primary ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of primary ciliary dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive primary ciliary dyskinesia confirmed in one individual, and probable primary ciliary dyskinesia identified in two others. The high prevalence of respiratory features compatible with primary ciliary dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory...

The rat dyskinesia model: neurochemical and behavioural characterisation; Das Rattendyskinesie-Modell: Neurochemische und verhaltenspharmakologische Charakterisierung

Buck, Kerstin
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
EN
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37.67%
Initially, therapy with the gold standard L-DOPA dramatically alleviates the cardinal symptoms of Parkinsons’s disease (PD) such as bradykinesia, rigidity and tremor and improves the quality of life of patients suffering from PD. However, long term use of L-DOPA can eventually result in serious treatment-limiting motor complications, namely dyskinesia which mainly comprises choreic and dystonic movements. The aim of my thesis was to gain insight into neurochemical and behavioural mechanisms underlying the expression of dyskinetic movements and thus characterise the rat L-DOPA dyskinesia model in depth. I shed light on various pathogenic factors, which contribute to the manifestation of L-DOPA-induced dyskinesia, as well as tested novel drug targets to obtain new strategies for the treatment of L-DOPA-induced dyskinesia. The results of my thesis demonstrated that the 6-OHDA rat dyskinesia model is a valuable and reliable model for both investigating mechanisms underlying L-DOPA-induced dyskinesia as well as identifying and validating novel drug targets. It is a well characterised model from the behavioural as well as molecular and biochemical side. The results from the present thesis demonstrate that 1) the neurotransmitter DA is instrumental for the manifestation of dyskinesia; 2) the DA-denervated striatum is the crucial brain area for L-DOPA-induced dyskinesia and 3) the noradrenergic systemic plays a role in dyskinesia...

Disordered respiration as a levodopa-induced dyskinesia in Parkinson's disease

Rice, J.; Antic, R.; Thompson, P.
Fonte: Wiley-Liss Publicador: Wiley-Liss
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
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37.05%
Symptomatic respiratory disturbance as a consequence of levodopa (L-dopa) therapy for Parkinson's disease (PD) has been described only rarely and may be underrecognized in clinical practice. We report on two patients with PD in whom the introduction or augmentation of L-dopa therapy was associated with the development of irregular and rapid breathing. Analysis of breathing patterns before and after L-dopa demonstrated a striking change in respiratory rate after administration of L-dopa, with the emergence of irregular tachypnea alternating with brief periods of apnea, in a pattern consistent with a central origin. In both cases, the temporal relationship of the respiratory disturbance to the administration of L-dopa suggested a peak-dose drug effect. Previous reports of L-dopa-induced respiratory dyskinesia are reviewed, and the potential mechanisms whereby L-dopa might influence the central control of respiration to produce irregular breathing patterns are discussed.; J.E. Rice, R. Antic, Philip D. Thompson; Copyright © 2002 Movement Disorders Society Published in Movement Disorders, 2002; 17 (3):524-527 at www.interscience.wiley.com

Schizophrenia, tardive dyskinesia and essential fatty acids

Vaddadi, K.S.; Gilleard, C.J.; Soosai, E.; Polonowita, A.K.; Gibson, R.A.; Burrows, G.D.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
Relevância na Pesquisa
37.05%
Several reports have indicated that people suffering from schizophrenia show an associated abnormality in levels of certain essential fatty acids (EFAs) in blood cells. Similar abnormalities have also been noted in association with the presence of tardive dyskinesia (TD). In order to study this further, 72 patients with the diagnosis of schizophrenia or schizoaffective disorder were examined to assess the relationship between psychiatric status, movement disorder (TD) and relative levels of the n-3 and n-6 essential fatty acids in red blood cell membranes and plasma. Patients were followed up over the next 4.5 years to determine whether or not changes in clinical state showed any systematic relationship to changes in essential fatty acid levels. We hypothesised that patients with schizophrenia would show persistently lowered levels of n-6 and n-3 series essential fatty acids, compared with normal controls. We further hypothesised that this abnormality would be greater in the presence versus absence of TD and the dominance of negative rather than positive symptoms. The only consistent findings were that lower levels of linoleic acid and higher levels of dihomogamma-linolenic acid characterised the patient population compared with control subjects but there was considerable variability in patients' EFA profile.; Krishna S. Vaddadi...

Neurophysiological Traces of L-Dopa Induced Dyskinesia in the Bed Nucleus Of The Stris Terminalis of 6-OHDA Lesioned Rats

Di Prospero, CYNTHIA
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
EN; EN
Relevância na Pesquisa
37.2%
The gold standard treatment for Parkinson’s disease (PD), L-3,4-dihydroxyphenylalanine (l-dopa), results in involuntary movements referred to as l-dopa-induced dyskinesia (LID). The mechanisms of LIDs are poorly known and there is no current strategy to efficiently prevent or control LIDs. Recent evidence has found that the expression of several immediate early genes positively correlates with LID severity in a basal forebrain structure, the bed nucleus of the stria terminalis (BNST). Furthermore, evidence shows that dopamine D1-like receptor (D1R)-dependent overexpression of IEGs in the oval (ov) and juxtacapsular (jx) subregions of the BNST may contribute to this phenomenon. Therefore this study aimed to examine how a D1R agonist modulates synaptic transmission in the ov and jxBNST of rats with and without LIDs using in vitro electrophysiology. Male Sprague Dawley rats (n=34) surgically received unilateral 6-OHDA lesions (2.5 µl at 3µg/µl) in the medial forebrain bundle. Three weeks after lesioning and upon occurrence of PD symptoms as measured by a stepping test, rats received daily injections of saline, or l-dopa (6mg/kg, i.p.) in benserazide (15mg/kg, i.p.), or benserazide alone. Benserazide is a peripheral inhibitor of DOPA-decarboxylase used to increase the central availability of dopamine (DA) and is generally administered with l-dopa...

Placebo Influences on Dyskinesia in Parkinson's Disease

Goetz, Christopher G.; Laska, Eugene; Hicking, Christine; Damier, Philippe; Müller, Thomas; Nutt, John; Olanow, C. Warren; Rascol, Olivier; Russ, Hermann
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/04/2008 EN
Relevância na Pesquisa
27.64%
Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo-associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo-related dyskinesia improvements and worsening. Because placebo-associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subjects received placebo treatment; 178 met criteria for placebo-associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo-associated improvement...

The Challenges of Diagnosing Primary Ciliary Dyskinesia

Leigh, Margaret W.; O'Callaghan, Christopher; Knowles, Michael R.
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
37.05%
Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic assays. The “gold standard” diagnostic test is ultrastructural analysis of respiratory cilia obtained by nasal scrape or brush biopsy. A few specialized centers use high-speed videomicroscopy to examine ciliary beat. Certain beat patterns correlate with ultrastructural defects, and, in some cases, subtle alterations in beat pattern can be seen when ultrastructure is normal. Recent studies have shown that nasal nitric oxide (NO) is very low in patients with PCD compared with healthy control subjects; therefore, this assay may be a useful screening or adjunctive test for PCD. Because acute respiratory illnesses may yield alterations in ciliary ultrastructure, ciliary beat, and nasal NO values, these tests should be performed during a stable baseline period. Identification of an array of PCD genes has provided the opportunity for making a definitive genetic diagnosis for PCD in some cases. All of these approaches have a role in diagnosing PCD. For example, PCD has been confirmed by identifying disease-causing mutations in a heavy dynein chain gene in individuals with normal ciliary ultrastructure but subtle defects in ciliary beat and low nasal NO. Priorities to improve nongenetic diagnostic capability include standardization of nasal NO as a screening test and the development of specialized centers using uniform approaches for the analysis of ciliary ultrastructure and ciliary beat pattern. Another chapter in this issue (see Zariwala and colleagues...

Building a predictive modeling system for sentence classification: a case study using tardive dyskinesia

Bi, Xia
Fonte: University of Delaware Publicador: University of Delaware
Tipo: Tese de Doutorado
Relevância na Pesquisa
37.05%
Wu, Cathy H.; Advances in computational and biological methods have greatly accelerated the pace of scientific discovery and produced a tremendous amount of experimental and computational data in the biomedical domain. Given the wealth of information that are available both in scientific papers and electronic databases, one particular challenge in biomedicine is to detect disease-drug associations and to organize them in a meaningful way that will accelerate pharmacogenetic research. Several text mining tools have been developed to facilitate this purpose. They perform adequately well in identifying facts and entities using on-the-fly search of scientific articles from many different databases; however, they cannot analyze the type of relationship that exist between the objects identified. In this thesis, we propose a novel method to analyze drug-disease relationships using a combination of in-house and open-source tools that exploit the Multinomial Naïve Bayes (MNB) modeling technique. The main motivation behind this thesis work is to assist researchers to quickly identify disease-drug relationships from the biomedical literature using the case study of tardive dyskinesia (TD) and to classify those relationships into specific categories to enable better understanding of various drug effects. We have manually developed and annotated a biomedical training corpus for TD via sentence classification. Using the MNB modeling technique...

Treatment of tardive dyskinesia: a systematic review (1997-2011)

Alimi,M.; Gaillard,P.; Camus,V.; El-Hage,W.
Fonte: The European Journal of Psychiatry Publicador: The European Journal of Psychiatry
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/09/2013 ENG
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37.2%
Background and Objectives: Tardive dyskinesia (TD) is a frequent and incapacitating side effect of first-generation antipsychotics. Although second-generation antipsychotics (SGAs) seem to be associated with a decreased risk of TD, it remains a severe, unresolved iatrogenic condition. Moreover, there is no commonly accepted effective treatment for TD. We conducted a systematic review of the literature to assess evidence regarding the effectiveness of different therapeutic interventions for TD. Methods: We performed a systematic review focussing exclusively on randomised controlled trials (RCTs). We searched the MEDLINE database (1997 to 2011) using the keyword "tardive dyskinesia" within the "title" search field. Twenty-six RCTs were included. Based on the evidence from RCTs, we built a decision tree that healthcare professionals can use to choose an effective therapeutic intervention for TD. Results: Four therapeutic interventions were found to be effective in TD (vitamin B6, ginkgo biloba, branched-chain amino acids, and piracetam). Conclusions: Patients with TD could benefit from the therapeutic interventions supported by the data accumulated from RCTs.

Effectiveness of melatonin in tardive dyskinesia

Castro,Fernando; Carrizo,Edgardo; Prieto de Rincón,Dexy; Rincón,Ciro Alberto; Asián,Triana; Medina-Leendertz,Shirley; Bonilla,Ernesto
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2011 EN
Relevância na Pesquisa
37.05%
Tardive Dyskinesia (TD) is a movement disorder associated with the clinical administration of antipsychotics. It is believed that TD is due, among other factors, to an increase in the oxidative damage produced by free radicals. Antioxidants, like vitamin E, have been used in the treatment of TD but there is no evidence of their effectiveness. Melatonin (MEL) is 6 to 10 times more effective, as an antioxidant, than vitamin E and it has been used with an apparent higher effectiveness in the treatment of TD, although the results have not been conclusive. A randomized, double blind, placebo controlled design was used to determine the effectiveness of MEL (20mg/day) during 12 weeks in 7 patients with TD. Six patients with TD were treated with placebo. The Abnormal Involuntary Movement Scale (AIMS) was chosen to assess the severity of TD initially and after 4, 8 and 12 weeks. The psychiatric evaluation was done following the Brief Psychiatric Rating Scale. In two patients treated with MEL a significant improvement (more than 60%) of the values of AIMS was detected. In the remainder five, as well as in the patients treated with placebo, no difference was observed during the 12 weeks. When compared the AIMS score in all the MEL-treated patients with the values in the placebo-treated patients...