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1.
Int J Cardiol ; 330: 43-49, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571563

RESUMO

BACKGROUND: Pregnant women with repaired tetralogy of Fallot (rTOF) are at increased risk of adverse outcomes. Although pre-pregnancy pulmonary valve replacement (PVR) may be considered in some women to attenuate risk, published data to support this practice are lacking. Our objective was to explore the impact of pre-pregnancy PVR on pregnancy outcomes in rTOF. METHODS: Women with rTOF and cardiovascular magnetic resonance imaging (CMR) before and after pregnancy were included if CMR studies were completed within 3 years of pregnancy. Subjects were compared according to presence (+) or absence (-) of PVR at pre-pregnancy CMR. Pregnancy outcomes (cardiovascular, obstetric, and fetal/neonatal) were documented. RESULTS: Of the 29 study women identified, 7 were PVR+ and 22 were PVR-. Post-pregnancy, the PVR- group demonstrated interval increase in indexed right ventricular end-diastolic volumes (RVEDVi) (157 ± 28 versus 166 ± 33 ml/m2, p = 0.003) and end-systolic volumes (RVESVi) (82 ± 17 versus 89 ± 20 ml/m2, p = 0.003) as compared with pre-pregnancy, but no significant change in RV ejection fraction, RV mass, or left ventricular measurements. In the PVR+ group, there were no interval changes in RV measurements pre-versus post pregnancy. Interval rate of change in RVESVi of PVR- exceeded PVR+ women (+3.7 ± 5.0 versus -2.2 ± 5.0 ml/m2/year, p = 0.03). Pregnancy outcomes did not differ in PVR+ versus PVR- women. CONCLUSIONS: Pregnancy outcomes did not differ according to PVR status in our cohort. While RV volumes remained unchanged in PVR+ women, interval RV dilation was observed in PVR- women. Additional study of a larger population with longer follow-up may further inform clinical practice regarding pre-pregnancy PVR.

2.
Appl Ergon ; 90: 103147, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32866688

RESUMO

PURPOSE: This study investigates the effects of the usage of a novel camera system compared to a conventional lens system for manual precision tasks. Utilizing the novel camera system aims to improve neck posture, reduce neck muscle tension and thereby minimize the risk of neck pain. METHODS: Camera and lens systems were compared by assessing the craniovertebral angle (CVA), electromyographic activity of the M.trapezius and perceived exertion. 16 healthy participants (n = 8 female, 24 ± 2 years; n = 8 male, 30 ± 5 years) performed manual precision tasks in a cross-over design using both systems in sitting and standing positions. RESULTS: Analyses showed that using the camera system improved the CVA in sitting [28.4° (22.8°-33.9°) to 42.5° (38.9°-46.1°); p < 0.01] and decreased the M.trapezius activity in standing [13.1% (7.7%-18.6%) to 8.65% (5.49%-11.81%)]. Additionally, overall and neck specific perceived exertion decreased when using the camera system in standing. CONCLUSIONS: The camera system may prevent neck pain in workers performing manual precision tasks in sitting and standing postures.

3.
Pediatr Cardiol ; 41(8): 1795-1799, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32915291

RESUMO

Increasing numbers of women with repaired tetralogy of Fallot (rTOF) are reaching reproductive age and seek counseling regarding their cardiovascular risks related to pregnancy. Therefore, the aim of this study was to characterize changes in left ventricular (LV) strain in women with rTOF during pregnancy and in the postpartum period. Seventeen pregnancies in women with rTOF were included (mean age at repair = 3.2 years ± 5.5 years; mean age at delivery = 32.7 ± 4 years). Echocardiograms from three time periods were analyzed; baseline (prior to conception or in the first trimester), third trimester, and 4-6 weeks postpartum. Sixty-five percent of the patients had at least mild pulmonary regurgitation. Eight patients (47%) had undergone at least one pulmonary valve replacement. There were no changes in LV ejection fraction (EF) or circumferential strain across the three time periods. Significant differences were present in longitudinal strain within the three time points (p = 0.01). Postpartum strain decreased in magnitude compared to the third trimester value (- 17.7 ± 4.1 vs. - 21 ± 5, p-value = 0.003) but was not different when compared to baseline strain (- 17.7 ± 4.1 vs. - 19.4 ± 3.4; p-value = 0.15). In conclusion, in women with rTOF, changes in longitudinal strain were observed during pregnancy with a return to baseline after delivery; EF did not change. These findings provide evidence that pregnancy does not adversely impact LV mechanics in the short term in this potentially vulnerable patient population.

4.
JAMA Neurol ; 76(2): 211-216, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508028

RESUMO

Importance: Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy. Objective: To determine the efficacy of GPi-DBS in a cohort of patients with XDP in a prospective study and identify predictors of postoperative outcomes. Design, Setting, and Participants: This observational prospective cohort study enrolled patients in February 2013 and was completed in December 2014. The patients were followed up for up to 46 months. Patients from the Philippines were treated in a single center in Lübeck, Germany and followed up in the Philippines. Sixteen men with XDP (mean [SD] age, 40.9 [7.3] years; disease duration, 1-6 years) from the Philippines with predominant dystonia were selected. Exposures: All patients underwent bilateral GPi-DBS in Lübeck, Germany. Main Outcomes and Measures: Clinical assessment included the motor parts of the Burke-Fahn-Marsden scale (BFMDRS-M) and the Unified Parkinson's Disease Rating Scale (UPDRS-III). T1-based basal ganglia volumetry was performed and correlated with postoperative outcomes. Results: The study participants included 16 Filipino men (mean age, 40.9 years). Masked video ratings revealed significant improvements of dystonia severity 1 week (-55%; range, -94% to 59%; P < .01) and 6 months (-59%; range, -100% to 22%; P < .001) after surgery. The UDPRS-III score also improved, albeit to a lesser extent (-19%; range, -54% to 95%; and -27%; range, -70% to 124%; respectively). Unmasked long-term follow-up confirmed the continued efficacy of GPi-DBS up to 46 months after surgery. Important secondary end points improved, including activities of daily living, pain severity, weight, and quality of life. Caudate atrophy was a predictor of a less beneficial outcome (r = 0.817, P = .004). Conclusions and Relevance: Internal globus pallidus DBS had a positive association in XDP with predominant dystonia (the primary end point) and contributed to an improved quality of life (the secondary end point). The response to DBS occurred within 1 week. Given the inverse correlation of postoperative benefit and caudate atrophy, GPi-DBS should be considered early during the disease course. Close international collaboration, training, and funding from multiple sources enabled the sustainable follow-up of patients with XDP in the Philippines.


Assuntos
Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Globo Pálido , Adulto , Núcleo Caudado/patologia , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Filipinas
5.
J Neurol ; 263(4): 730-4, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26872670

RESUMO

Specific mutations in COL6A3 have recently been reported as the cause of isolated recessive dystonia, which is a rare movement disorder. In all patients, at least one mutation was located in Exons 41 and 42. In an attempt to replicate these findings, we assessed by direct sequencing the frequency of rare variants in Exons 41 and 42 of COL6A3 in 955 patients with isolated or combined dystonia or with another movement disorder with dystonic features. We identified nine heterozygous carriers of rare variants including five different missense mutations and an extremely rare synonymous variant. In these nine patients, we sequenced the remaining 41 coding exons of COL6A3 to test for a second mutation in the compound heterozygous state. In only one of them, a second rare variant was identified (Thr732Met + Pro3082Arg). Of note, this patient had been diagnosed with Parkinson´s disease (with dystonic posturing) due to homozygous PINK1 mutations. The COL6A3 mutations clearly did not segregate with the disease in the four affected siblings of this family. Further, there was no indication for a disease-modifying effect of the COL6A3 mutations since disease severity or age at onset did not correlate with the number of COL6A3 mutated alleles in this family. In conjunction with the relatively high frequency of homozygous carriers of reported mutations in publically available databases, our data call a causal role for variants in COL6A3 in isolated dystonia into question.


Assuntos
Colágeno Tipo VI/genética , Distúrbios Distônicos/genética , Mutação , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem
7.
Gut ; 65(3): 512-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25661083

RESUMO

OBJECTIVE: The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). DESIGN: Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). RESULTS: In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. CONCLUSIONS: Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool.


Assuntos
Engenharia Celular/métodos , Hepacivirus/imunologia , Hepatite C/terapia , Imunoterapia/métodos , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Proteínas do Envelope Viral/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Células Cultivadas , Hepatite C/imunologia , Hepatite C/virologia , Hepatócitos/imunologia , Hepatócitos/virologia , Humanos
8.
Behav Neurol ; 2015: 961372, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26351406

RESUMO

BACKGROUND: Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population. OBJECTIVE: To assess depressive symptoms in PD patients and control groups and compare symptom profiles. METHODS: After postal screening of 10,000 citizens of Lübeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects. Based on motor examinations, we distinguished PD patients, Healthy Controls (HC, no motor impairment), and Disease Controls (DC, motor impairment other than PD). RESULTS: The sample comprised 331 men and 311 women, aged 65 ± 8 years. Out of the overall sample, 198 (41.5%) had a BDI score ≥9. BDI results above 9 points occurred in 34.5% of HC, 50.3% of DC, and 42.4% of PD patients. Compared to the control groups (HC, DC) the PD patients endorsed more "dissatisfaction" and "loss of appetite" but less "feelings of guilt," "self-hate," and "loss of libido." CONCLUSION: Depressive symptoms are more frequent in PD patients compared to HC but not DC. Interestingly, the distribution of individual symptoms of the BDI differs between groups with an emphasis on loss of pleasure/enjoyment in the PD group, a symptom typically considered to be dopaminergically transmitted.


Assuntos
Depressão/fisiopatologia , Doença de Parkinson/fisiopatologia , Idoso , Depressão/epidemiologia , Depressão/etiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Pesquisa Qualitativa
9.
Mov Disord ; 30(4): 531-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25546094

RESUMO

The prerequisite for an earlier diagnosis of Parkinson's disease (PD) are markers that are both sensitive and specific for clinically definite PD and its prediagnosic phases. Promising candidates include enlarged hyperechogenicity of the substantia nigra (SN+) on transcranial sonography (TCS) and hyposmia. However, despite good sensitivity and specificity, both markers have yet failed to yield reliable predictions. We pursue the possibility of combined use in an ongoing population-based cohort. Subjects were recruited from 10,000 inhabitants of Luebeck/Germany aged 50 to 79 years and additional PD patients from our outpatient clinic. After neurological examination, 715 subjects were grouped into clinically definite PD (n = 106), possible prediagnostic PD (ppPD; n = 73), and a control group subdivided into healthy individuals (n = 283) and controls with diseases other than PD (n = 253). Subjects underwent TCS and smell testing. Sensitivity and specificity of SN+ and hyposmia were good for PD; however, positive predictive values (PPV) of both SN+ (5.2%) and olfaction (2.5%) were low. At least one positive/both positive markers were present in 33%/1% of healthy controls, 33%/2% of diseased controls, 62%/7% of ppPD, and 94%/51% of PD. When combining SN+ and hyposmia, PPV increased to 17.6%, with a sensitivity of 51% and a specificity of 98%. Both SN+ and hyposmia offer good enrichment towards PD and ppPD, are stable against other diseases, and the combination of markers highly increases specificity. However, if the combination of SN+ and hyposmia were used as criterion for PD diagnosis, almost half of clinically definite PD and more than 90% of ppPD would have been missed.


Assuntos
Transtornos do Olfato/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Substância Negra/patologia , Idade de Início , Idoso , Planejamento em Saúde Comunitária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Substância Negra/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
10.
Neuropsychologia ; 62: 38-47, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25038550

RESUMO

Patients with Parkinson׳s disease (PD) respond more readily than healthy controls to irrelevant stimuli that contain task-relevant, response-priming features. This behavior may reflect oversensitivity to response-relevant features of irrelevant stimuli or failure to select relevant stimuli. To decide between these alternatives, we investigated in a "contingent-capture" paradigm whether PD patients are also oversensitive to task-relevant features that do not prime responses. PD patients and healthy controls had to report the orientation of bars in target color, presented among bars of other colors. Critically, target arrays were preceded by arrays of rings, all gray except one which might be the target color and might be presented at the same position as the upcoming target. Replicating earlier results from young healthy participants (Eimer, Kiss, Press, & Sauter, 2009), signal rings in target color induced an N2pc component over contralateral visual cortex and some positivity at anterior sites (d-P200), both indicative of attentional capture. Correspondingly, signals in target color facilitated correct responding to upcoming targets presented at the same location and impeded correct responses otherwise. Patients with PD had diminished N2pc, lacked the frontal focus of d-P200, and their responses tended to be less affected than healthy participants' by signal position. Thus PD patients appeared less affected than healthy persons by stimuli with relevant features. This outcome is compatible with the notion that PD patients have poorer internal representations of what is relevant in a given task.


Assuntos
Atenção/fisiologia , Doença de Parkinson/complicações , Transtornos da Percepção/etiologia , Detecção de Sinal Psicológico/fisiologia , Percepção Visual/fisiologia , Adulto , Idoso , Análise de Variância , Eletroencefalografia , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Orientação , Transtornos da Percepção/diagnóstico , Estimulação Luminosa
11.
Parkinsonism Relat Disord ; 20(6): 608-12, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24661467

RESUMO

Reluctance to start medication has never been investigated before in PD. We studied reluctance to start medication for PD motor symptoms, namely its prevalence, underlying reasons, drug-specificity, and associated delay in the start of PD medication. A cross-sectional observational international study was conducted. Patients with a clinical diagnosis of PD advised to start antiparkinsonian medication in the previous 5 years were invited to complete a questionnaire in three centers located in North America and Europe. An electronic online survey was sent to physicians through the mailing list of the Movement Disorder Society. 469 participants (201 PD patients, 268 physicians). 40.2% (n = 82) of the patients reported reluctance to start medication, but 88.6% (n = 234/264) of the physicians estimated that ≤20% of their patients with PD had been reluctant to start medication. The most common reasons reported by patients were the fear of side effects (n = 35, 55.6%), followed by non-acceptance of diagnosis (n = 23, 36.5%); fear of a temporally limited benefit was more commonly selected by physicians (n = 92/267, 34.5%). Patients indicated reluctance to start DAs more frequently compared with L-DOPA (OR: 2.22, 95% CI: 1.30, 9.03; p = 0.013) while physicians perceived L-DOPA to be associated with more reluctance (OR: 4.7, 95% CI: 3.41; 6.59; p < 0.0001). Patients with PD and physicians have a different perspective on the issue of reluctance to start medication. There is a need to bring physicians and patients with PD closer to a shared vision of the problem reluctance to start medication.


Assuntos
Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Relações Médico-Paciente , Médicos/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Inquéritos e Questionários
12.
JAMA Neurol ; 71(4): 490-4, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24535567

RESUMO

IMPORTANCE: Mutations in the GNAL gene have recently been shown to cause primary torsion dystonia. The GNAL-encoded protein (Gαolf) is important for dopamine D1 receptor function and odorant signal transduction. We sequenced all 12 exons of GNAL in 461 patients from Germany, Serbia, and Japan, including 318 patients with dystonia (190 with cervical dystonia), 51 with hyposmia and Parkinson disease, and 92 with tardive dyskinesia or acute dystonic reactions. OBSERVATIONS: We identified the following two novel heterozygous putative mutations in GNAL: p.Gly213Ser in a German patient and p.Ala353Thr in a Japanese patient. These variants were predicted to be pathogenic in silico, were absent in ethnically matched control individuals, and impaired Gαolf coupling to D1 receptors in a bioluminescence energy transfer (BRET) assay. Two additional variants appeared to be benign because they behaved like wild-type samples in the BRET assay (p.Ala311Thr) or were detected in ethnically matched controls (p.Thr92Ala). Both patients with likely pathogenic mutations had craniocervical dystonia with onset in the fifth decade of life. No pathogenic mutations were detected in the patients with hyposmia and Parkinson disease, tardive dyskinesias, or acute dystonic reactions. CONCLUSIONS AND RELEVANCE: Mutations in GNAL can cause craniocervical dystonia in different ethnicities. The BRET assay may be a useful tool to support the pathogenicity of identified variants in the GNAL gene.


Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP/genética , Mutação/genética , Torcicolo/etiologia , Torcicolo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Criança , Feminino , Alemanha/etnologia , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Sérvia/etnologia , Torcicolo/etnologia , Adulto Jovem
13.
Parkinsonism Relat Disord ; 20(4): 428-31, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24444533

RESUMO

BACKGROUND: Dopa-responsive dystonia (DRD) is a young-onset neurometabolic disorder often presenting with a combination of parkinsonism and dystonia. The pathophysiology includes an impairment of dopaminergic and serotonergic neurotransmission. Uncontrolled reports suggest an increased frequency of neuropsychiatric abnormalities and sleep impairment. METHODS: In 23 GCH1 mutation-positive DRD patients and 26 healthy controls, non-motor features and their effect on the quality of life (QoL) were assessed. Six patients underwent polysomnography (PSG). RESULTS: Depressive and anxiety symptoms were not more common among DRD patients. Average sleep quality was similar across groups. This was also true for self-reported mean sleep onset (27.5 vs. 27.1 min) and total sleep time (6.5 vs. 6.6 h). Upon PSG, the number of spontaneous arousals was increased in four patients. QoL was impaired with respect to physical health. Sleep impairment and depressive but not anxiety symptoms were associated with lower QoL. CONCLUSION: The present results do not confirm the clinical impression and biologically plausible assumption of an increased frequency of non-motor symptoms in DRD. The impairment of QoL is associated with a decline of the physical condition only but not with other factors.


Assuntos
Distúrbios Distônicos/complicações , Distúrbios Distônicos/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polissonografia , Inquéritos e Questionários , Adulto Jovem
14.
Eur J Health Econ ; 15(5): 477-87, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23793870

RESUMO

Group purchasing organizations gain increasing importance with respect to the supply of pharmaceutical products and frequently use multiple, exclusive or partially exclusive rebate contracts to exercise market power. Based on a Hotelling model of horizontal and vertical product differentiation, we examine the controversy around whether a superior rebate scheme exists, as far as consumer surplus, firms' profits and total welfare are concerned. We find that firms clearly prefer partially exclusive over multiple, and multiple over exclusive rebate contracts. In contrast, no rebate form exists that lowers total costs per se for the consumers or maximizes total welfare.


Assuntos
Contratos/economia , Assistência à Saúde/organização & administração , Indústria Farmacêutica/organização & administração , Compras em Grupo/organização & administração , Marketing de Serviços de Saúde/organização & administração , Assistência à Saúde/economia , Indústria Farmacêutica/economia , Compras em Grupo/economia , Humanos , Marketing de Serviços de Saúde/economia , Modelos Econômicos
15.
Mov Disord ; 29(7): 921-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24375517

RESUMO

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P < 10(-5) and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP (P < 5 × 10(-8) ) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P = 3.95 × 10(-9) ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD (P = 2.78 × 10(-2) ) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λ = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients.


Assuntos
Arilsulfatases/genética , Distúrbios Distônicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Desempenho Psicomotor/fisiologia , Loci Gênicos , Testes Genéticos/métodos , Humanos , Risco , Fatores de Risco
16.
J Pept Sci ; 19(7): 415-22, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23649726

RESUMO

The 2-(o-nitrophenyl)-propyl (NPP) group is used as caging group to mask the nucleobases adenine and cytosine in N-(2-aminoethyl)glycine peptide nucleic acids (aeg-PNA). The adeninyl and cytosinyl nucleo amino acid building blocks Fmoc-a(NPP) -aeg-OH and Fmoc-c(NPP) -aeg-OH were synthesized and incorporated into PNA sequences by Fmoc solid phase synthesis relying on high stability of the NPP nucleobase protecting group toward Fmoc-cleavage, coupling, capping, and resin cleavage conditions. Removal of the nucleobase caging group was achieved by UV-LED irradiation at 365 nm. The nucleobase caging groups provided sterical crowding effecting the Watson-Crick base pairing, and thereby, the PNA double strand stabilities. Duplex formation can completely be suppressed for complementary PNA containing caging groups in both strands. PNA/PNA recognition can be completely restored by UV light-triggered release of the photolabile protecting group.


Assuntos
Luz , Ácidos Nucleicos Peptídicos/química , Estrutura Molecular , Ácidos Nucleicos Peptídicos/síntese química , Temperatura , Raios Ultravioleta
17.
Int J Epidemiol ; 42(1): 128-128k, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23257687

RESUMO

Parkinson's disease is increasingly viewed as a complex disorder including a range of typical non-motor symptoms in addition to the cardinal motor signs. This cohort was set up in 2010 to investigate the specificity of non-motor symptoms for Parkinson's disease. For this, we included several control groups with decreasing contrast from Parkinson's disease patients. Group definitions ranged from healthy control subjects to those with suspected early motor signs of parkinsonism. Using a mailed questionnaire, we screened 5838 inhabitants of Lübeck, Germany, out of a target population of 10 000 citizens, enquiring about motor impairment, pain, quality of life, comorbidities, somatization and demographics. Based on this information, participants were assigned to screening groups, and selected participants were invited for in-person examination (n = 623). The examination included cognitive examinations, transcranial ultrasound, a brief psychiatric interview and a standardized motor examination that was used to assign examination groups. In addition, all participants answered questionnaires addressing depression, anxiety, sleep and quality of life. The first-year follow-up examination was performed either in person using the same protocol or via mailed questionnaires. This study is ongoing and publications are in preparation, but you may contact the first author (meike.kasten@neuro.uni-luebeck.de) with suggestions for collaboration or data requests.


Assuntos
Depressão/epidemiologia , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Vigilância da População/métodos , Transtornos das Sensações/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Depressão/etiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Atividade Motora , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico , Doença de Parkinson/psicologia , Prevalência , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Transtornos das Sensações/etiologia , Transtornos do Sono-Vigília/etiologia , Fatores Socioeconômicos , Inquéritos e Questionários , Ultrassonografia Doppler Transcraniana
18.
Mov Disord ; 27(8): 1012-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22693071

RESUMO

Patients with Parkinson's disease (PD) have difficulties in the control of self-guided (i.e., internally driven) movements. The basal ganglia provide a nonspecific internal cue for the development of a preparatory activity for a given movement in the sequence of repetitive movements. Controversy surrounds the question of whether PD patients are capable of (1) anticipating (before an external trigger appears; i.e., anticipation) and (2) predicting movement velocity once a moving target shortly disappears from the visual scene (i.e., prediction). To dissociate between these two components, we examined internally driven (extraretinal generated) smooth pursuit eye movements in PD patients and age-matched healthy controls by systematically varying target blanking periods of a trapezoidally moving target in four paradigms (initial blanking, midramp blanking, blanking after a short ramp, and no blanking). Compared to controls, PD patients showed (1) decreased smooth pursuit gain (without blanking), (2) deficient anticipatory pursuit (prolonged pursuit initiation latency; reduced eye velocity before target onset in the early onset blanking paradigm), and (3) preserved extraretinal predictive pursuit velocity (midramp target blanking). Deficient anticipation of future target motion was not related to either disease duration or the general motor impairment (UPDRS). We conclude that PD patients have difficulties in anticipating future target motion, which may play a role for the mechanisms involved in deficient gait initiation and termination of PD. In contrast, they remain unimpaired in their capacity of building up an internal representation of continuous target motion. This may explain the clinical advantage of medical devices that use visual motion to improve gait initiation (e.g., "PD glasses").


Assuntos
Antecipação Psicológica , Transtornos da Motilidade Ocular/fisiopatologia , Doença de Parkinson/fisiopatologia , Acompanhamento Ocular Uniforme , Movimentos Sacádicos , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/psicologia , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Desempenho Psicomotor
19.
Am J Clin Nutr ; 90(6): 1509-16, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19812175

RESUMO

BACKGROUND: High-protein diets are effective for weight reduction; however, little is known about the potential adverse renal effects of such diets. OBJECTIVE: The aim of our study was to compare the effect of a high-protein (HP) with a normal-protein (NP) diet on renal hemodynamics and selected clinical-chemical factors. DESIGN: We prospectively studied the effect of an HP diet (2.4 g x kg(-1) x d(-1)) with that of an NP diet (1.2 g x kg(-1) x d(-1)) on the glomerular filtration rate (assessed on the basis of sinistrin-an inulin analog-clearance) and renal plasma flow (para-aminohippuric acid clearance) by using the constant infusion technique. Filtration fraction and renal vascular resistance were calculated. Twenty-four healthy young men followed the 2 diet protocols for 7 d each in a crossover design. They were individually advised by a dietitian to achieve the planned protein intake by selecting normal foods under isocaloric conditions. Serum and urinary variables and renal hemodynamics were measured on day 7 of both diets. RESULTS: The glomerular filtration rate (NP: 125 +/- 5 mL/min; HP: 141 +/- 8 mL/min; P < 0.001) and filtration fraction (NP: 23 +/- 5%; HP: 28 +/- 5%; P < 0.05) increased significantly with the HP diet. Renal plasma flow was not significantly different between the HP (496 +/- 25 mL/min) and NP (507 +/- 18 mL/min) phases. Renal vascular resistance was not significantly different between the NP (94 +/- 6 mm Hg x mL(-1) x min(-1)) and HP (99 +/- 8 mm Hg x mL(-1) x min(-1)) phases. Blood urea nitrogen, serum uric acid, glucagon, natriuresis, urinary albumin, and urea excretion increased significantly with the HP diet. CONCLUSIONS: A short-term HP diet alters renal hemodynamics and renal excretion of uric acid, sodium, and albumin. More attention should be paid to the potential adverse renal effects of HP diets.


Assuntos
Proteínas na Dieta/administração & dosagem , Taxa de Filtração Glomerular , Hemodinâmica , Adulto , Albuminúria/etiologia , Pressão Sanguínea , Estudos Cross-Over , Humanos , Masculino , Estudos Prospectivos , Fluxo Plasmático Renal , Ácido Úrico/urina , Resistência Vascular
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