The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study.

PubMed

Factor, Stewart A; Remington, Gary; Comella, Cynthia L; Correll, Christoph U; Burke, Joshua; Jimenez, Roland; Liang, Grace S; O'Brien, Christopher F

Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period. The extension phase was conducted from December 16, 2014, to August 3, 2016. Participants who received placebo and entered the VE period were re-randomized 1:1 to valbenazine 80 or 40 mg while others continued valbenazine at the KINECT 3 dose. Safety assessments included treatment-emergent adverse events (TEAEs) and scales for suicidal ideation/behavior, treatment-emergent akathisia or parkinsonism, and psychiatric symptoms. Efficacy assessments included the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD). 198 participants entered the VE period, 124 (62.6%) completed treatment (week 48), and 121 (61.1%) completed the follow-up visit after washout (week 52). During the VE period, 69.2% of participants had ≥ 1 TEAE, 14.6% had a serious TEAE, and 15.7% discontinued due to a TEAE. During washout, 13.1% of participants experienced a TEAE. No apparent risk for suicidal ideation or behavior was found. Long-term valbenazine treatment did not appear to induce or worsen akathisia or parkinsonism. Participants generally remained psychiatrically stable during the study. AIMS and CGI-TD measures indicated sustained tardive dyskinesia improvement, with scores returning toward baseline after 4 weeks of valbenazine washout. The long-term safety and tolerability of valbenazine were generally favorable, and maintenance of treatment effect was apparent with both doses during this long-term study. ClinicalTrials.gov identifier: NCT

Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia.

PubMed

Modestin, J; Stephan, P L; Erni, T; Umari, T

2000-05-05

In 200 inpatients on regular neuroleptics, point prevalence of extrapyramidal syndromes, including Parkinson syndrome, akathisia and tardive dyskinesia (TD), was studied and found to be 20, 11 and 22%, respectively. A total of 46 patients have currently, and for a longer time, (average about 3years, median over 1year) been treated with clozapine, and 127 with typical neuroleptics (NLs). Comparing both groups, higher TD scores were found in the clozapine sample. Investigating the influence of a set of seven clinical variables on the TD score with the help of multiple regression analysis, the influence of the treatment modality disappeared, whereas the age proved to be the only significant variable. Studying the role of past clozapine therapy in patients currently on typical NLs and comparing 10 matched pairs of chronic patients with and without TD in whom a complete life-time cumulative dose of NLs was identified, a relationship between TD and length of current typical NL therapy and life-time typical NL dosage could be demonstrated. On the whole, long-term relatively extensive use of clozapine has not markedly reduced the prevalence of extrapyramidal syndromes in our psychiatric inpatient population. In particular, we failed to demonstrate a beneficial effect of clozapine on prevalence of TD. There are certainly patients who suffer from TD in spite of a long-term intensive clozapine treatment.

Measuring neuroleptic-induced akathisia by three-channel actometry.

PubMed

Tuisku, K; Lauerma, H; Holi, M; Markkula, J; Rimon, R

1999-11-30

Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.

Inhibitory motor dysfunction in parkinson's disease subtypes.

PubMed

Gong, Tao; Xiang, Yuanyuan; Saleh, Muhammad G; Gao, Fei; Chen, Weibo; Edden, Richard A E; Wang, Guangbin

2018-06-01

Parkinson's disease (PD) is divided into postural instability gait difficulty (PIGD) and tremor-dominant (TD) subtypes. Increasing evidence has suggested that the GABAergic neurotransmitter system is involved in the pathogenesis of PD. To evaluate the differences of GABA levels between PD motor subtypes using MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS). COHORT.: SUBJECTS: PD patients were classified into PIGD (n = 13) and TD groups (n = 9); 16 age- and sex-matched healthy controls were also recruited. All subjects were right-handed. All subjects underwent an magnetic resonance spectroscopy scan including MEGA-PRESS at 3.0T. The detected GABA signal also contains signal from macromolecules (MM) and homocarnosine, so it is referred to as GABA+. GABA + levels and Creatine (Cr) levels were quantified in the left basal ganglia (BG) using Gannet 2.0 by Tao Gong. Differences in GABA + levels between the three groups were analyzed using analysis of covariance. The relationship between GABA levels and a unified PD rating scale (UPDRS) was also analyzed. GABA + levels were significantly lower in left BG regions of PD patients compared with healthy controls (P < 0.001). In PD patients, the GABA concentration was lower in the TD group than the PIGD group (P = 0.019). Cr levels in PIGD and TD were lower than controls (P = 0.020; P = 0.002). A significant negative correlation was found in PIGD between GABA levels and UPDRS (r = -0.572, P = 0.041), while no correlation was found in TD (r = -0.339, P = 0.372). Low BG GABA levels in PD patients, and differences between PIGD/TD patients, suggest that GABAergic dysfunction may play an important role in the pathogenesis of Parkinson's disease. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1610-1615. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of Antipsychotic Type and Dose Changes on Tardive Dyskinesia and Parkinsonism Severity in Patients With a Serious Mental Illness: The Curaçao Extrapyramidal Syndromes Study XII.

PubMed

Mentzel, Charlotte L; Bakker, P Roberto; van Os, Jim; Drukker, Marjan; Matroos, Glenn E; Hoek, Hans W; Tijssen, Marina A J; van Harten, Peter N

2017-03-01

To test the efficacy of current treatment recommendations for parkinsonism and tardive dyskinesia (TD) severity in patients with severe mental illness (SMI). We present an 18-year prospective study including all 223 patients with SMI (as defined by the 1987 US National Institute of Mental Health, which were based on DSM-III-R diagnostic criteria) receiving care from the only psychiatric hospital of the former Netherlands Antilles. Eight clinical assessments (1992-2009) focused on movement disorders and medication use. Tardive dyskinesia was measured by the Abnormal Involuntary Movement Scale and parkinsonism by the Unified Parkinson's Disease Rating Scale. Antipsychotics were classified into first-generation antipsychotic (FGA) versus second-generation antipsychotic (SGA) and high versus low dopamine 2 (D₂) affinity categories. The effect that switching has within each category on subsequent movement scores was calculated separately by using time-lagged multilevel logistic regression models. There was a significant association between reduction in TD severity and starting/switching to an FGA (B = -3.54, P < .001) and starting/switching to a high D₂ affinity antipsychotic (B = -2.49, P < .01). Adding an SGA to existing FGA treatment was associated with reduction in TD severity (B = -2.43, P < .01). For parkinsonism, stopping antipsychotics predicted symptom reduction (B = -7.76, P < .01 in FGA/SGA-switch model; B = -7.74, P < .01 in D₂ affinity switch model), while starting a high D₂ affinity antipsychotic predicted an increase in symptoms (B = 3.29, P < .05 in D₂ affinity switch model). The results show that switching from an FGA to an SGA does not necessarily result in a reduction of TD or parkinsonism. Only stopping all antipsychotics reduces the severity of parkinsonism, and starting an FGA or a high D₂ affinity antipsychotic may reduce the severity of TD. © Copyright 2017 Physicians Postgraduate Press, Inc.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

PubMed

Katz, Maya; Luciano, Marta San; Carlson, Kimberly; Luo, Ping; Marks, William J; Larson, Paul S; Starr, Philip A; Follett, Kenneth A; Weaver, Frances M; Stern, Matthew B; Reda, Domenic J; Ostrem, Jill L

2015-04-01

The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation. © 2015 American Neurological Association.

Interdiffusion in the Ni/TD-NiCr and Cr/TD-NiCr systems

NASA Technical Reports Server (NTRS)

Pawar, A. V.; Tenney, D. R.

1974-01-01

The diffusion of Ni and Cr into TD-NiCr has been studied over the 900 to 1100 C temperature range. The diffusion couples were prepared by electroplating Cr and Ni on polished TD-NiCr wafers. Concentration profiles produced as a result of isothermal diffusion at 905, 1000, and 1100 C were determined by electron microprobe analysis. The Boltzmann-Matano analysis was used to determine concentration-dependent diffusion coefficients which were found to compare favorably with previously reported values. These data suggest that 2 vol % ThO2 distribution has no appreciable effect on the rates of diffusion in TD-NiCr with a large grain size. This supports the view that an inert dispersoid in an alloy matrix will not in itself lead to enhanced diffusion unless a short-circuit diffusion structure is stabilized.

Postural instability and gait are associated with severity and prognosis of Parkinson disease.

PubMed

van der Heeden, Jorine F; Marinus, Johan; Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Geraedts, Victor J; van Hilten, Jacobus J

2016-06-14

Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications. Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365). The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results. In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself. © 2016 American Academy of Neurology.

Levodopa response differs in Parkinson's motor subtypes: A task-based effective connectivity study.

PubMed

Mohl, Brianne; Berman, Brian D; Shelton, Erika; Tanabe, Jody

2017-06-15

Parkinson's disease (PD) is a circuit-level disorder with clinically-determined motor subtypes. Despite evidence suggesting each subtype may have different pathophysiology, few neuroimaging studies have examined levodopa-induced differences in neural activation between tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtype patients during a motor task. The goal of this functional MRI (fMRI) study was to examine task-induced activation and connectivity in the cortico-striatal-thalamo-cortical motor circuit in healthy controls, TD patients, and PIGD patients before and after levodopa administration. Fourteen TD and 12 PIGD cognitively-intact patients and 21 age- and sex-matched healthy controls completed a right-hand, paced tapping fMRI paradigm. Collectively, PD patients off medication (OFF) showed hypoactivation of the motor cortex relative to healthy controls, even when controlling for performance. After levodopa intake, the PIGD patients had significantly increased activation in the left putamen compared with TD patients and healthy controls. Psychophysiological interaction analysis revealed that levodopa increased effective connectivity between the posterior putamen and other areas of the motor circuit during tapping in TD patients, but not in PIGD patients. This novel, levodopa-induced difference in the neural responses between PD motor subtypes may have significant implications for elucidating the mechanisms underlying the distinct phenotypic manifestations and enabling the classification of motor subtypes objectively using fMRI. © 2017 Wiley Periodicals, Inc.

Cyclic creep and fatigue of TD-NiCr (thoria-dispersion-strengthened nickel-chromium), TD-Ni, and NiCr sheet at 1200 C

NASA Technical Reports Server (NTRS)

Hirschberg, M. H.; Spera, D. A.; Klima, S. J.

1972-01-01

The resistance of thin TD-NiCr sheet to cyclic deformation was compared with that of TD-Ni and a conventional nickel-chromium alloy. Strains were determined by a calibration technique which combines room-temperature strain gage and deflection measurements with high-temperature deflection measurements. Analyses of the cyclic tests using measured tensile and creep-rupture data indicated that the TD-NiCr and NiCr alloy specimens failed by a cyclic creep mechanism. The TD-Ni specimens, on the other hand, failed by a fatigue mechanism.

S4. ASYMMETRIC DRUG-INDUCED PARKINSONISM IS RELATED TO PSYCHOPATHOLOGY

PubMed Central

Pieters, Lydia; Bakker, P Roberto; Van Harten, Peter N

2018-01-01

severity index (CGI-SCH SI). Discussion DIP is asymmetric in 1 of 5 patients. Therefore, the clinical rule that Parkinson’s disease always starts asymmetrically and such may be helpful to differentiate between Parkinson’s disease and DIP is not valid. Asymmetric presentation of DIP is of clinical relevance as it is related to the severity of psychopathology. Asymmetric DIP may alert the clinician of more severe psychopathology. Replication is indicated to examine the robustness of the relationship. References 1. Modestin J, Wehrli MV, Stephan PL, Agarwalla P. Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment. Schizophr Res. 2008; 100(1–3): 97–107. 2. Janno S, Holi M, Tuisku K, Wahlbeck K. Prevalence of Neuroleptic-Induced Movement Disorders in Chronic Schizophrenia Inpatients. Am J Psychiatry. 2004; 161(1): 160–163. 3. Harten PN Van, Matroos GE, Hoek HW. The prevalence of tardive dystonia, tardive dyskinesia, parkinsonism and akathisia. The Curaçao Extrapyramidal Syndromes Study I. Schizophr Res. 1996; 19(2): 195–203. 4. Shin H, Chung J. Drug-Induced Parkinsonism. J Clin Neurol. 2012; 8: 15–21. 5. Bakker PR, de Groot IW, van Os J, van Harten PN. Long-Stay Psychiatric Patients: A Prospective Study Revealing Persistent Antipsychotic-Induced Movement Disorder. PLoS One. 2011; 6(10): 1–6.

Parkinson subtype-specific Granger-causal coupling and coherence frequency in the subthalamic area.

PubMed

Florin, Esther; Pfeifer, Johannes; Visser-Vandewalle, Veerle; Schnitzler, Alfons; Timmermann, Lars

2016-09-22

Previous work on Parkinson's disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor-periods and non-tremor-periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4-8Hz and 8-12Hz, respectively. However, when considering only tremor-periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients. Copyright © 2016

Fluctuating Cotard syndrome in a patient with advanced Parkinson disease.

PubMed

Solla, Paolo; Cannas, Antonino; Orofino, Gianni; Marrosu, Francesco

2015-02-01

Nonmotor fluctuations of psychiatric symptoms in patients suffering from Parkinson disease (PD) represent a very disabling condition, which may seriously interfere with the quality of life of patients and caregivers. In this regard, these disturbances are present with a higher frequency in advanced PD patients with associated motor complications and can appear both in "on" and in "off" period. Here we report on a case of fluctuating Cotard syndrome clearly related to "wearing-off" deterioration and responsive to levodopa treatment in a patient affected by advanced PD. A 76-year-old woman presented with a 13-year history of PD. Her caregivers reported that, in the last 2 months, she has developed a sudden onset of nihilistic delusion (Cotard syndrome), mainly during the "wearing-off" condition and associated with end of dose dyskinesias and akathisia.As Cotard syndrome clearly improved with the administration of levodopa, the patient was successfully treated changing the levodopa schedule with the shortening of intervals between levodopa intakes in small doses. Both the appearance of the Cotard syndrome in this patient during the "off" state and the subsequent improvement of psychotic symptoms after levodopa administration strongly suggest an important correlation with the dopaminergic dysregulation.This finding suggests that dopaminergic deficit might play a key factor in the development of Cotard syndrome.

Travellers' diarrhoea: Impact of TD definition and control group design on study results.

PubMed

Lääveri, Tinja; Pakkanen, Sari H; Kirveskari, Juha; Kantele, Anu

2018-02-02

Travellers' diarrhoea (TD) is a common health problem among visitors to the (sub)tropics. Much research deals with aetiology, prevention, and post-infection sequalae, yet the data may not allow comparisons due to incompatible definitions of TD and No TD control groups. The impact of defining TD and No TD control groups was explored by revisiting our recent data. We set up two TD groups: classical TD i.e. ≥3 loose or liquid stools/day and WHO TD (diarrhoea as defined by the WHO) i.e. any diarrhoea, and four No TD groups by TD definition and timing (no classical/WHO TD during travel, no ongoing classical/WHO TD). TD was recorded for 37% versus 65% of subjects when using classical versus WHO definitions, respectively; the proportions of the various pathogens proved similar. The strictest criterion for the No TD control group (no WHO TD during travel) yielded pathogens among 61% and the least strict (no ongoing classical TD) among 73% of the travellers; the differences were greatest for enteroaggregative Escherichia coli and Campylobacter. Definition of TD and control group design substantially impact on TD study results. The WHO definition yields more cases, but the pathogen selection is similar by both definitions. Design of the No TD control group was found critical: only those remaining asymptomatic throughout the journey should be included. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tetanus, Diphtheria (Td) Vaccine

MedlinePlus

... Headache (about 1 person in 4) Tiredness (about 1 person in 4) Moderate Problems following Td vaccine:(Interfered with activities, but did not require medical attention)Fever over 102°F (rare) Severe Problems following ...

TdT activity in acute myeloid leukemias defined by monoclonal antibodies.

PubMed

San Miguel, J F; González, M; Cañizo, M C; Anta, J P; Portero, J A; López-Borrasca, A

1986-09-01

Blast cells from eight out of 71 patients diagnosed with acute myeloid leukemia (AML) by morphological, cytochemical, and immunological criteria showed TdT activity. Their distribution according to the FAB classification was one M1, one M2, one M4, two M5a, one M5b, one M6, and one undifferentiated case. The TdT+ AML cases did not show major clinical and hematological differences when compared with the classical TdT- AML patients. Other phenotypical aberrations in the expression of membrane antigens, apart from the presence of nuclear TdT, were not observed in these TdT+ cases after study with a large panel of monoclonal antibodies. A higher incidence of TdT+ cases was found among the monocytic variants of AML (M4 and M5)--four cases--than in the granulocytic variants (M1, M2, and M3)--2 cases. These TdT+ cases should be distinguished from mixed leukemias by double labeling techniques, assessing in the TdT+ AML the coexpression of TdT and myeloid markers in individual cells as shown in four of our cases.

Long-range correction for tight-binding TD-DFT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humeniuk, Alexander; Mitrić, Roland, E-mail: roland.mitric@uni-wuerzburg.de

2015-10-07

We present two improvements to the tight-binding approximation of time-dependent density functional theory (TD-DFTB): First, we add an exact Hartree-Fock exchange term, which is switched on at large distances, to the ground state Hamiltonian and similarly to the coupling matrix that enters the linear response equations for the calculation of excited electronic states. We show that the excitation energies of charge transfer states are improved relative to the standard approach without the long-range correction by testing the method on a set of molecules from the database in Peach et al. [J. Chem. Phys. 128, 044118 (2008)] which are known tomore » exhibit problematic charge transfer states. The degree of spatial overlap between occupied and virtual orbitals indicates where TD-DFTB and long-range corrected TD-DFTB (lc-TD-DFTB) can be expected to produce large errors. Second, we improve the calculation of oscillator strengths. The transition dipoles are obtained from Slater Koster files for the dipole matrix elements between valence orbitals. In particular, excitations localized on a single atom, which appear dark when using Mulliken transition charges, acquire a more realistic oscillator strength in this way. These extensions pave the way for using lc-TD-DFTB to describe the electronic structure of large chromophoric polymers, where uncorrected TD-DFTB fails to describe the high degree of conjugation and produces spurious low-lying charge transfer states.« less

Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed?

PubMed

Citrome, Leslie

2012-07-01

To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH). Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism. NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5

Exact PsTd invariant and PsTd symmetric breaking solutions, symmetry reductions and Bäcklund transformations for an AB-KdV system

NASA Astrophysics Data System (ADS)

Jia, Man; Lou, Sen Yue

2018-05-01

In natural and social science, many events happened at different space-times may be closely correlated. Two events, A (Alice) and B (Bob) are defined as correlated if one event is determined by another, say, B = f ˆ A for suitable f ˆ operators. A nonlocal AB-KdV system with shifted-parity (Ps, parity with a shift), delayed time reversal (Td, time reversal with a delay) symmetry where B =Ps ˆ Td ˆ A is constructed directly from the normal KdV equation to describe two-area physical event. The exact solutions of the AB-KdV system, including PsTd invariant and PsTd symmetric breaking solutions are shown by different methods. The PsTd invariant solution show that the event happened at A will happen also at B. These solutions, such as single soliton solutions, infinitely many singular soliton solutions, soliton-cnoidal wave interaction solutions, and symmetry reduction solutions etc., show the AB-KdV system possesses rich structures. Also, a special Bäcklund transformation related to residual symmetry is presented via the localization of the residual symmetry to find interaction solutions between the solitons and other types of the AB-KdV system.

Tree Data (TD)

Treesearch

Robert E. Keane

2006-01-01

The Tree Data (TD) methods are used to sample individual live and dead trees on a fixed-area plot to estimate tree density, size, and age class distributions before and after fire in order to assess tree survival and mortality rates. This method can also be used to sample individual shrubs if they are over 4.5 ft tall. When trees are larger than the user-specified...

Uplink scheduling and adjacent-channel coupling loss analysis for TD-LTE deployment.

PubMed

Yeo, Woon-Young; Moon, Sung Ho; Kim, Jae-Hoon

2014-01-01

TD-LTE, one of the two duplexing modes in LTE, operates in unpaired spectrum and has the advantages of TDD-based technologies. It is expected that TD-LTE will be more rapidly deployed in near future and most of WiMax operators will upgrade their networks to TD-LTE gradually. Before completely upgrading to TD-LTE, WiMax may coexist with TD-LTE in an adjacent frequency band. In addition, multiple TD-LTE operators may deploy their networks in adjacent bands. When more than one TDD network operates in adjacent frequency bands, severe interference may happen due to adjacent channel interference (ACI) and unsynchronized operations. In this paper, coexistence issues between TD-LTE and other systems are analyzed and coexistence requirements are provided. This paper has three research objectives. First, frame synchronization between TD-LTE and WiMax is discussed by investigating possible combinations of TD-LTE and WiMax configurations. Second, an uplink scheduling algorithm is proposed to utilize a leakage pattern of ACI in synchronized operations. Third, minimum requirements for coexistence in unsynchronized operations are analyzed by introducing a concept of adjacent-channel coupling loss. From the analysis and simulation results, we can see that coexistence of TD-LTE with other TDD systems is feasible if the two networks are synchronized. For the unsynchronized case, some special cell-site engineering techniques may be required to reduce the ACI.

Uplink Scheduling and Adjacent-Channel Coupling Loss Analysis for TD-LTE Deployment

PubMed Central

Yeo, Woon-Young; Moon, Sung Ho

2014-01-01

TD-LTE, one of the two duplexing modes in LTE, operates in unpaired spectrum and has the advantages of TDD-based technologies. It is expected that TD-LTE will be more rapidly deployed in near future and most of WiMax operators will upgrade their networks to TD-LTE gradually. Before completely upgrading to TD-LTE, WiMax may coexist with TD-LTE in an adjacent frequency band. In addition, multiple TD-LTE operators may deploy their networks in adjacent bands. When more than one TDD network operates in adjacent frequency bands, severe interference may happen due to adjacent channel interference (ACI) and unsynchronized operations. In this paper, coexistence issues between TD-LTE and other systems are analyzed and coexistence requirements are provided. This paper has three research objectives. First, frame synchronization between TD-LTE and WiMax is discussed by investigating possible combinations of TD-LTE and WiMax configurations. Second, an uplink scheduling algorithm is proposed to utilize a leakage pattern of ACI in synchronized operations. Third, minimum requirements for coexistence in unsynchronized operations are analyzed by introducing a concept of adjacent-channel coupling loss. From the analysis and simulation results, we can see that coexistence of TD-LTE with other TDD systems is feasible if the two networks are synchronized. For the unsynchronized case, some special cell-site engineering techniques may be required to reduce the ACI. PMID:24707214

A G protein-coupled receptor (GPCR) in red: live cell imaging of the kappa opioid receptor-tdTomato fusion protein (KOPR-tdT) in neuronal cells

PubMed Central

Huang, Peng; Chiu, Yi-Ting; Chen, Chongguang; Wang, Yujun; Liu-Chen, Lee-Yuan

2013-01-01

Introduction In contrast to green fluorescent protein and variants (GFPs), red fluorescent proteins (RFPs) have rarely been employed for generation of GPCR fusion proteins, likely because of formation of aggregates and cell toxicity of some RFPs. Among all the RFPs available, tdTomato (tdT), one of the non-aggregating RFP, has the highest brightness score (about 3 times that of eGFP) and unsurpassed photostability. Methods We fused tdT to the KOPR C-terminus. The KOPR-tdT cDNA construct was transfected into Neuro2A mouse neuroblastoma cell line (Neuro2A cells) and rat cortical primary neurons for characterization of pharmacological properties and imaging studies on KOPR trafficking. Results KOPR-tdT retained KOPR properties (cell surface expression, ligand binding, agonist-induced signaling and internalization) when expressed in Neuro2A cells and rat primary cortical neurons. Live cell imaging of KOPR-tdT enables visualization of time course of agonist-induced internalization of KOPR in real time for 60 min, without photobleaching and apparent cell toxicity. U50,488H-induced KOPR internalization occurred as early as 4 min and plateaued at about 30 min. A unique pattern of internalized KOPR in processes of primary neurons was induced by U50,488H. Discussion tdT is an alternative to, or even a better tool than, GFPs for fusing to GPCR for trafficking studies, because tdT has higher brightness and thus better resolution and less photobleaching problems due to reduced laser power used. It also has advantages associated with its longer-wavelength emission including spectral separation from autofluorescence and GFPs, reduced cell toxicity the laser may impose, and greater tissue penetration. These advantages of tdT over GPFs may be critical for live cell imaging studies of GPCRs in vitro and for studying GPCRs in vivo because of their low abundance. PMID:23856011

Parkinson's Disease

MedlinePlus

... Staying Safe Videos for Educators Search English Español Parkinson's Disease KidsHealth / For Kids / Parkinson's Disease What's in this ... symptoms of something called Parkinson's disease. What Is Parkinson's Disease? Parkinson's disease is a disorder of the central ...

The Efficiency of Delone Coverings of the Canonical Tilings T^*(A4) and T}(*(D_6)) -> T^*(D6)

NASA Astrophysics Data System (ADS)

Papadopolos, Zorka; Kasner, Gerald

This chapter is devoted to the coverings of the two quasiperiodic canonical tilings T^*(A4) and T}(*(D_6)) equiv {cal T}(*(2F)) -> T^*(D6) T^*(2F), obtained by projection from the root lattices A4 and D6, respectively. In the first major part of this chapter, in Sect. 5.2, we shall introduce a Delone covering C^sT^*(A4) of the 2-dimensional decagonal tiling T^*(A4). In the second major part of this chapter, Sect. 5.3, we summarize the results related to the Delone covering of the icosahedral tiling T}(*(D_6)) -> T^*(D6), T}(*(D_6)}) -> CT^*(D6) and determine the zero-, single-, and double- deckings and the resulting thickness of the covering. In the conclusions section, we give some suggestions as to how the definition of the Delone covering might be changed in order to reach some real (full) covering of the icosahedral tiling T}(*(D_6)) -> T^*(D6). In Section 5.2 the definition of the Delone covering is also changed in order to avoid an unnecessary large thickness of the covering.

Deformation and annealing response of TD-nickel chromium sheet

NASA Technical Reports Server (NTRS)

Kane, R. D.; Ebert, L. J.

1973-01-01

The deformation and annealing response of TD-nickel chromium (TD-NiCr) 0.1 inch thick sheet was examined using various cold-rolling and annealing treatments. Upon annealing (above 816 C (1500 F), the as-received material was converted from an initially ultra-fine grain size (average grain dimension 0.51 micron) to a large grain structure. Increases in grain size by a factor of 100 to 200 were observed for this transformation. However, in those material states where the large grain transformation was absent, a fine grain recrystallized structure formed upon annealing (above 732 C (1350 F)). The deformation and annealing response of TD-NiCr sheet was evaluated with respect to the processing related variables as mode and severity of deformation and annealing temperature. Results indicate that the large grain transformation, classical primary recrystallization occurs. Using selected materials produced during the deformation and annealing study, the elevated temperature tensile properties of TD-NiCr sheet were examined in the temperature range 593 C (1100 F) to 1093 C (2000 F). It was observed that the elevated temperature tensile properties of TD-NiCr sheet could be optimized by the stabilization of a large grain size in this material using the cold working and/or annealing treatments developed during the present investigation.

Many-Body Perturbation Theory (MBPT) and Time-Dependent Density-Functional Theory (TD-DFT): MBPT Insights About What Is Missing In, and Corrections To, the TD-DFT Adiabatic Approximation.

PubMed

Casida, Mark E; Huix-Rotllant, Miquel

2016-01-01

In their famous paper, Kohn and Sham formulated a formally exact density-functional theory (DFT) for the ground-state energy and density of a system of N interacting electrons, albeit limited at the time by certain troubling representability questions. As no practical exact form of the exchange-correlation (xc) energy functional was known, the xc-functional had to be approximated, ideally by a local or semilocal functional. Nowadays, however, the realization that Nature is not always so nearsighted has driven us up Perdew's Jacob's ladder to find increasingly nonlocal density/wavefunction hybrid functionals. Time-dependent (TD-) DFT is a younger development which allows DFT concepts to be used to describe the temporal evolution of the density in the presence of a perturbing field. Linear response (LR) theory then allows spectra and other information about excited states to be extracted from TD-DFT. Once again the exact TD-DFT xc-functional must be approximated in practical calculations and this has historically been done using the TD-DFT adiabatic approximation (AA) which is to TD-DFT very similar to what the local density approximation (LDA) is to conventional ground-state DFT. Although some of the recent advances in TD-DFT focus on what can be done within the AA, others explore ways around the AA. After giving an overview of DFT, TD-DFT, and LR-TD-DFT, this chapter focuses on many-body corrections to LR-TD-DFT as one way to build hybrid density-functional/wavefunction methodology for incorporating aspects of nonlocality in time not present in the AA.

Motor assessment in Parkinson`s disease.

PubMed

Opara, Józef; Małecki, Andrzej; Małecka, Elżbieta; Socha, Teresa

2017-09-21

Parkinson's disease (PD) is one of most disabling disorders of the central nervous system. The motor symptoms of Parkinson's disease: shaking, rigidity, slowness of movement, postural instability and difficulty with walking and gait, are difficult to measure. When disease symptoms become more pronounced, the patient experiences difficulties with hand function and walking, and is prone to falls. Baseline motor impairment and cognitive impairment are probable predictors of more rapid motor decline and disability. An additional difficulty is the variability of the symptoms caused by adverse effects of drugs, especially levodopa. Motor assessment of Parkinson`s Disease can be divided into clinimetrics, assessment of balance and posture, arm and hand function, and gait/walking. These are many clinimetric scales used in Parkinson`s Disease, the most popular being the Hoehn and Yahr stages of progression of the disease and Unified Parkinson's Disease Rating Scale. Balance and posture can be assessed by clinimetric scales like the Berg BS, Tinetti, Brunel BA, and Timed Up and Go Test, or measured by posturometric platforms. Among skill tests, the best known are: the Purdue Pegboard Test, Nine-Hole Peg Test, Jebsen and Taylor test, Pig- Tail Test, Frenchay Arm Test, Action Research Arm Test, Wolf FMT and Finger-Tapping Test. Among motricity scales, the most popular are: the Fugl-Meyer Motor Assessment Scale and Södring Motor Evaluation. Gait and walking can also be assessed quantitatively and qualitatively. Recently, the most popular is three-dimensional analysis of movement. This review article presents the current possibilities of motor assessment in Parkinson`s disease.

[Local brain activity in different motor subtypes of Parkinson's disease with fMRI].

PubMed

Hou, Ya'nan; Zhang, Jiarong; Chen, Biao; Wu, Tao

2015-02-17

To explore the changes of local brain activity in motor subtypes of Parkinson's disease (PD) with functional magnetic resonance imaging (fMRI). A total of 60 idiopathic PD and 30 age- and gender-matched normal controls were examined with resting-state fMRI from January 2013 to March 2014. All subjects gave their written informed consent for the study. The amplitude of low-frequency fluctuation (ALFF) was calculated to measure local brain activity. The PD patients were divided into two groups of tremor dominant (TD) and postural instability/gait difficulty (PIGD) (n = 30 each). All subjects gave their written in formed consent for the study.One-way ANOVA and post-hoc t-test were performed to detect the differences of local brain activity between PD and normal subjects. And the correlations were examined between ALFF, scores and levodopa dose. Compared with normal subjects, the TD group showed increased activity in bilateral cerebellums (-37, -47, -38), thalamus (-18, -17,0), pons (-3, -23, -37) and left precentral gyrus (-41, -30, 46) versus decreased activity in bilateral frontal lobes (-13, 69, 6), temporal lobes (-42, 18, -21), left insula (-32, 22, 2) and left anterior cingulated (-7, 32, -5). The PIGD group showed increased activity in right postcentral gyrus (63, -18, 39) and decreased activity in bilateral putamens (-24, 12, 3), pre-supplementary motor area (10, 10, 58), frontal lobes (15, -15, 57), temporal lobes (-39, 18, -3) and left insula (-29, 20, 11). Compared with PIGD, the TD group showed increased activity in temporal lobes, but decreased activity in frontal lobes. Additionally, ALFF in bilateral cerebellums and frontal lobes was positively correlated with TD scores while ALFF in left precentral gyrus, bilateral putamens and temporal lobes negatively correlated with TD scores. ALFF in bilateral frontal lobes and left temporal lobe was positively correlated with PIGD scores.However, in right postcentral gyrus and bilateral putamens, ALFF was

Functional heterogeneity of memory B lymphocytes: in vivo analysis of TD-primed B cells responsive to secondary stimulation with TD and TI antigens.

PubMed

Rennick, D M; Morrow, P R; Benjamini, E

1983-08-01

The functional heterogeneity of memory B cells induced by a single determinant, consisting of a decapeptide representing amino acid residues 103-112 of tobacco mosaic virus protein (TMVP), was analyzed. Decapeptide specific antibodies were elicited in mice adoptively transferred with TMVP-immune spleen cells when challenged with TMVP, decapeptide conjugated to succinylated human gamma-globulin (SHGG), or decapeptide conjugated to Brucella abortus (BA). Whereas secondary stimulation by either TMVP or decapeptide-SHGG was dependent on appropriately primed T cells, stimulation by decapeptide-BA was independent of conventional T cell help. Furthermore, memory B cells responsive to TMVP (TD), decapeptide-SHGG (TD), or decapeptide-BA (TI. 1 prototype) were shown to consist of overlapping populations because adoptive recipients of TMVP-primed cells challenged simultaneously with TD and TI decapeptide antigens did not result in a higher antibody response than that elicited by one of the TD antigens injected alone. However, decapeptide-BA consistently induced a smaller antidecapeptide response than either TMVP or decapeptide-SHGG. This suggested that only a fraction of the memory B cell population which was activated by the original priming antigen (thymus-dependent) was also responsive to secondary in vivo stimulation by the priming hapten conjugated to Brucella abortus. Detailed analyses of the antibodies induced in the recipients of TMVP-immune spleen cells after secondary challenge with either TMVP, decapeptide-SHGG, or decapeptide-BA failed to distinguish between the responsive memory B cells; the antidecapeptide antibodies induced by all three immunogens shared the same fine specificities and immunoglobulin isotype composition. These data are viewed as further evidence that subsets of TD-primed B cells, which may display differential sensitivity to cross-stimulation with TD and TI forms of the antigen, represent distinct stages of memory B cell maturation within a

Describing excited state relaxation and localization in TiO 2 nanoparticles using TD-DFT

DOE PAGES

Berardo, Enrico; Hu, Han -Shi; van Dam, Hubertus J. J.; ...

2014-02-26

We have investigated the description of excited state relaxation in naked and hydrated TiO 2 nanoparticles using Time-Dependent Density Functional Theory (TD-DFT) with three common hybrid exchange-correlation (XC) potentials; B3LYP, CAM-B3LYP and BHLYP. Use of TD-CAM-B3LYP and TD-BHLYP yields qualitatively similar results for all structures, which are also consistent with predictions of coupled cluster theory for small particles. TD-B3LYP, in contrast, is found to make rather different predictions; including apparent conical intersections for certain particles that are not observed with TD-CAM-B3LYP nor with TD-BHLYP. In line with our previous observations for vertical excitations, the issue with TD-B3LYP appears to bemore » the inherent tendency of TD-B3LYP, and other XC potentials with no or a low percentage of Hartree-Fock Like Exchange, to spuriously stabilize the energy of charge-transfer (CT) states. Even in the case of hydrated particles, for which vertical excitations are generally well described with all XC potentials, the use of TD-B3LYP appears to result in CT-problems for certain particles. We hypothesize that the spurious stabilization of CT-states by TD-B3LYP even may drive the excited state optimizations to different excited state geometries than those obtained using TD-CAM-B3LYP or TD-BHLYP. In conclusion, focusing on the TD-CAM-B3LYP and TD-BHLYP results, excited state relaxation in naked and hydrated TiO 2 nanoparticles is predicted to be associated with a large Stokes’ shift.« less

Describing excited state relaxation and localization in TiO 2 nanoparticles using TD-DFT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berardo, Enrico; Hu, Han -Shi; van Dam, Hubertus J. J.

We have investigated the description of excited state relaxation in naked and hydrated TiO 2 nanoparticles using Time-Dependent Density Functional Theory (TD-DFT) with three common hybrid exchange-correlation (XC) potentials; B3LYP, CAM-B3LYP and BHLYP. Use of TD-CAM-B3LYP and TD-BHLYP yields qualitatively similar results for all structures, which are also consistent with predictions of coupled cluster theory for small particles. TD-B3LYP, in contrast, is found to make rather different predictions; including apparent conical intersections for certain particles that are not observed with TD-CAM-B3LYP nor with TD-BHLYP. In line with our previous observations for vertical excitations, the issue with TD-B3LYP appears to bemore » the inherent tendency of TD-B3LYP, and other XC potentials with no or a low percentage of Hartree-Fock Like Exchange, to spuriously stabilize the energy of charge-transfer (CT) states. Even in the case of hydrated particles, for which vertical excitations are generally well described with all XC potentials, the use of TD-B3LYP appears to result in CT-problems for certain particles. We hypothesize that the spurious stabilization of CT-states by TD-B3LYP even may drive the excited state optimizations to different excited state geometries than those obtained using TD-CAM-B3LYP or TD-BHLYP. In conclusion, focusing on the TD-CAM-B3LYP and TD-BHLYP results, excited state relaxation in naked and hydrated TiO 2 nanoparticles is predicted to be associated with a large Stokes’ shift.« less

A novel thiazolidinedione derivative TD118 showing selective algicidal effects for red tide control.

PubMed

Wu, Ying; Lee, Yew; Jung, Seul-Gi; Kim, Minju; Eom, Chi-Yong; Kim, Si Wouk; Cho, Hoon; Jin, Eonseon

2014-05-01

Thiazolidinedione (TD) derivatives have been found to have an algicidal effect on harmful algal bloom microalgae. In this study, 75 TD derivatives were synthesized and analyzed for algicidal activity. Among these synthetic TDs, 18 TD derivatives showed specific algicidal activity on two strains belonging to the classes Raphidophyceae (Chattonella marina and Heterosigma akashiwo) and Dinophyceae (Cochlodinium polykrikoides). Two strains belonging to Bacillariophyceae (Navicula pelliculosa and Phaeodactylum EPV), one strain belonging to Dinophyceae (Amphidinium sp.), and a Eustigmatophycean microalga (Nannochloropsis oculata) showed less sensitivity to the TD derivatives than the other two phyla. The most reactive TD derivative, compound 2 (TD118), was selected and tested for morphological and physiological changes. TD118 effectively damaged the cell membrane of C. marina, H. akashiwo and C. polykrikoides. The O₂ evolution and photosystem II efficiency (F(v)/F(m)) of C. marina, H. akashiwo and C. polykrikoides were also severely reduced by TD118 treatment. Amphidinium sp., N. pelliculosa, Phaeodactylum EPV and N. oculata showed less reduction of O₂ evolution and the F(v)/F(m) by TD118. These results imply that the species-specific TD structure relationship may be due to structural and/or physiological differences among microalgal species.

State-of-technology for joining TD-NiCr sheet.

NASA Technical Reports Server (NTRS)

Holko, K. H.; Moore, T. J.; Gyorgak, C. A.

1972-01-01

At the current state-of-technology there are many joining processes that can be used to make sound welds in TD-NiCr sheet. Some of these that are described in this report are electron beam welding (EBW), gas-tungsten arc welding (GTAW), diffusion welding (DFW), resistance spot welding (RSW), resistance seam welding (RSEW), and brazing. Roll welding (RW) and explosion welding (EXW) have not been developed to the point where they can be used to make sound welds in TD-NiCr. Joining work that has previously been done on TD-NiCr by various organizations, both privately supported and under Air Force and NASA contracts, is described in this summary. Current work is also described that is being done at General Dynamics/Convair (under NASA contract) and at NASA/Lewis to develop and evaluate DFW, RSW, RSEW, and brazing. Preliminary comparisons of joining processes are made for typical applications. A brief description of the manufacture of TD-NiCr sheet by a recently standardized process (under NASA contract) also is given.

Clinical risk factors for the development of tardive dyskinesia.

PubMed

Solmi, Marco; Pigato, Giorgio; Kane, John M; Correll, Christoph U

2018-06-15

Tardive dyskinesia (TD) is a severe condition that can affect almost 1 out of 4 patients on current or previous antipsychotic treatment, including both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). While two novel vesicular monoamine transporter inhibitors, deutetrabenazine and valbenazine, have shown acute efficacy for TD, the majority of patients do not remit, and TD appears to recur once treatment is withdrawn. Hence, prevention of TD remains a crucial goal. We provide a clinically oriented overview of risk factors for TD, dividing them into patient-, illness- and treatment-related variables, as well as nonmodifiable and modifiable factors. Unmodifiable patient-related and illness-related risk factors for TD include older age, female sex, white and African descent, longer illness duration, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related and treatment-related factors include diabetes, smoking, and alcohol and substance abuse, FGA vs SGA treatment, higher cumulative and current antipsychotic dose or antipsychotic plasma levels, early parkinsonian side effects, anticholinergic co-treatment, akathisia, and emergent dyskinesia. Clinicians using dopamine antagonists need to consider risk factors for TD to minimize TD and its consequences. Copyright © 2018 Elsevier B.V. All rights reserved.

Deformation and annealing response of TD-nickel chromium

NASA Technical Reports Server (NTRS)

Kane, R. D.; Ebert, L. J.

1975-01-01

The recrystallization and grain growth processes occurring in TD-NiCr were examined with respect to deformation severity, annealing time, and temperature. Results indicated that two different annealing responses of TD-NiCr are possible, depending on the initial state and processing history prior to annealing. As-received sheet showed a dramatic increase in grain size with decreasing annealing temperature, whereas sheet prior-annealed at 1316 C for 1 hr exhibited very little variation with subsequent annealing temperature.

Exploratory study of friction welds in Udimet 700 and TD-Nickel bar

NASA Technical Reports Server (NTRS)

Moore, T. J.

1971-01-01

Friction welded butt joints were made in both Udimet 700 and TD-Nickel bar. Also, dissimilar metal friction welds were made between these materials. Friction welding of Udimet 700 shows great promise because the welds were found to be as strong as the parent metal in stress rupture and tensile tests at 760 and 980 C. The weld line was not detectable metallographically in the heat treated condition. Friction welding for TD-Nickel, however, holds little if any promise. TD-Nickel friction weldments could support only 9 percent as much stress as the base metal for a 10-hour stress-rupture life at 1090 C. Dissimilar Udimet 700/TD-Nickel friction welds could sustain only 15 percent as much stress as the TD-Nickel parent metal for a 10-hour rupture life at 930 C.

Serum uric acid level and its association with motor subtypes and non-motor symptoms in early Parkinson's disease: PALS study.

PubMed

Huang, Xinxin; Ng, Samuel Yong-Ern; Chia, Nicole Shuang-Yu; Acharyya, Sanchalika; Setiawan, Fiona; Lu, Z-H; Ng, Ebonne; Tay, Kay-Yaw; Au, Wing-Lok; Tan, Eng-King; Tan, Louis Chew-Seng

2018-05-17

Uric acid has been found to be potentially neuroprotective in Parkinson's disease (PD). We investigated the relationship between serum uric acid levels and both motor and non-motor features in a prospective early PD cohort study. Fasting serum uric acid levels were measured from 125 early PD patients. Demographic, clinical characteristics, motor and non-motor assessments were performed. Patients were categorized into three motor subtypes: tremor-dominant (TD), postural instability/gait difficulty (PIGD), and mixed. Non-motor symptoms were classified as present or absent based on the appropriate cut-offs for each non-motor instrument. Most patients had TD (n = 51, 40.8%) and mixed (n = 63, 50.4%) motor subtypes, while a minority had PIGD (n = 11, 8.8%) motor subtype. The mean serum uric acid levels were significantly different between the three motor subtypes (p = 0.0106), with the mixed subtype having the lowest serum uric acid levels. Using the TD subtype as reference, patients with higher serum uric acid levels were less likely to have the mixed (OR = 0.684; p = 0.0312) subtype as opposed to the TD subtype. Uric acid levels were not significantly different between the TD and PIGD subtypes. For non-motor symptoms, higher serum uric acid levels were significantly associated with less fatigue (OR = 0.693; p = 0.0408). Higher serum uric acid levels were associated with TD motor subtype and less fatigue in early PD, which could be related to its anti-oxidative properties. Uric acid could be an important biomarker for specific motor features and symptoms of fatigue in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

TD-60 links RalA GTPase function to the CPC in mitosis

PubMed Central

Papini, Diana; Langemeyer, Lars; Abad, Maria A.; Kerr, Alastair; Samejima, Itaru; Eyers, Patrick A.; Jeyaprakash, A. Arockia; Higgins, Jonathan M. G.; Barr, Francis A.; Earnshaw, William C.

2015-01-01

TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore–microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies. PMID:26158537

Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes.

PubMed

Nyberg, Eric M; Tanabe, Jody; Honce, Justin M; Krmpotich, Theodore; Shelton, Erika; Hedeman, Jessica; Berman, Brian D

2015-05-01

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 T high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p = 0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p = 0.06). While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Secondary parkinsonism

MedlinePlus

... developing. Alternative Names Parkinsonism - secondary; Atypical Parkinson disease Images Central nervous system and peripheral nervous system References Jankovic J. Parkinson disease and other movement disorders. In: Daroff ...

Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.

PubMed

Janno, Sven; Holi, Matti; Tuisku, Katinka; Wahlbeck, Kristian

2004-01-01

Since most of the world's schizophrenia patients are treated with conventional antipsychotics, the authors evaluated various methods for establishing the prevalence of neuroleptic-induced movement disorders in these patients. DSM-IV criteria and established score thresholds on a movement disorder rating scale were used to identify cases of neuroleptic-induced movement disorder in a representative Estonian patient sample of 99 chronic institutionalized schizophrenia patients, 18-65 years old, treated with conventional neuroleptics (79.8%) or clozapine (20.2%). Neuroleptic-induced movement disorders according to DSM-IV criteria were found in 61.6% of the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence rates for akathisia and tardive dyskinesia were similar when either DSM-IV criteria or rating scale scores were used, but the prevalence rate for parkinsonism was much lower per DSM-IV criteria than according to rating scale score. Nearly two-thirds of chronic schizophrenia patients suffered from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse effects still impose a huge burden on the majority of neuroleptic-treated individuals with schizophrenia. The discrepancy between the standard identification methods for neuroleptic-induced movement disorder indicate the need for further research.

Tremor analysis separates Parkinson's disease and dopamine receptor blockers induced parkinsonism.

PubMed

Shaikh, Aasef G

2017-05-01

Parkinson's disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson's disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor). Cycle-by-cycle analysis was performed to measure cycle duration, oscillation amplitude, and inter-cycle variations in the frequency. Patients with dopamine receptor blocker induced parkinsonism had lower resting and postural tremor amplitude. There was a substantial increase of kinetic tremor amplitude in both disorders. Postural and resting tremor in subjects with dopamine receptor blocking agent-induced parkinsonism was prominent in the abduction-adduction plane. In contrast, the Parkinson's disease tremor had equal amplitude in all three planes of motion. Tremor frequency was comparable in both groups. Remarkable variability in the width of the oscillatory cycles suggested irregularity in the oscillatory waveforms in both subtypes of parkinsonism. Quantitative tremor analysis can distinguish Parkinson's disease from dopamine receptor blocking agent-induced parkinsonism.

Transceiver Multiplexers TD-1288( )/GRC and TD-1289( )(V)/GRC.

DTIC Science & Technology

1982-02-01

TRASITCAS TD-1289( )iV)1/GRC C.76 IR BANPAS FLER TERMINATION UNIT CU26()/GRC] G -42 RC MX-10080t )/GRC F’igure l-l. X1liF’ MultipleXer amily Tree. F1- CU-2266...the equations become: Y G o t Q 1Q+/Qu C o s 0 = j2 + Q QU L° l~ Qu I+j L=010 log 4 + j 2 Qt The passband loss expression may be simplified to read: 4...a character istic impedance of 50 oims. The linle len,_tli was 16i.5 inches and was tet oiinated inl a -ohio If load. The tap pointt was nojusted to g

Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.

PubMed

Cooper, Christine A; Jain, Nimansha; Gallagher, Michael D; Weintraub, Daniel; Xie, Sharon X; Berlyand, Yosef; Espay, Alberto J; Quinn, Joseph; Edwards, Karen L; Montine, Thomas; Van Deerlin, Vivianna M; Trojanowski, John; Zabetian, Cyrus P; Chen-Plotkin, Alice S

2017-01-01

Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross-sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha-synuclein ( SNCA ) expression in the GTEx (Genotype-Tissue Expression project) consortium database. Genotype at rs356182, near SNCA , correlated with the TD/PIGD ratio in both the discovery (Bonferroni-corrected P = 0.04) and replication cohorts ( P = 0.02). The rs356182 GG genotype was associated with a more tremor-predominant phenotype and predicted a slower rate of motor progression (1-point difference in annual rate of UPDRS-III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum ( P = 0.005). Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor-predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA . Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.

Characterization of Thermophilic Halotolerant Aeribacillus pallidus TD1 from Tao Dam Hot Spring, Thailand

PubMed Central

Yasawong, Montri; Areekit, Supatra; Pakpitchareon, Arda; Santiwatanakul, Somchai; Chansiri, Kosum

2011-01-01

The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The cell was 2.0–40 μm in length and about 0.4 μm in diameter. The optimum growth occurred at 55–60 °C and at pH 7–8. Strain TD1 was able to grow on medium containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty acid content was mainly C16:0, which comprised 25.04% of the total amount of cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM 3670T. Bayesian tree analysis strongly supported the idea that strain TD1 is affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM 3670T, some physiological properties and the cellular fatty acid profiles differ significantly. A. pallidus strain TD1 can produce extracellular pectate lyase, which has not been reported elsewhere for other bacterial strains in the genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate lyase producer, which may have useful industrial applications. PMID:21954359

Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease.

PubMed

He, Naying; Huang, Pei; Ling, Huawei; Langley, Jason; Liu, Chunlei; Ding, Bei; Huang, Juan; Xu, Hongmin; Zhang, Yong; Zhang, Zhongping; Hu, Xiaoping; Chen, Shengdi; Yan, Fuhua

2017-04-01

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Elevated temperature deformation of TD-nickel base alloys

NASA Technical Reports Server (NTRS)

Petrovic, J. J.; Kane, R. D.; Ebert, L. J.

1972-01-01

Sensitivity of the elevated temperature deformation of TD-nickel to grain size and shape was examined in both tension and creep. Elevated temperature strength increased with increasing grain diameter and increasing L/D ratio. Measured activation enthalpies in tension and creep were not the same. In tension, the internal stress was not proportional to the shear modulus. Creep activation enthalpies increased with increasing L/D ratio and increasing grain diameter, to high values compared with that of the self diffusion enthalpy. It has been postulated that two concurrent processes contribute to the elevated temperature deformation of polycrystalline TD-nickel: (1) diffusion controlled grain boundary sliding, and (2) dislocation motion.

TD-1792 versus Vancomycin for Treatment of Complicated Skin and Skin Structure Infections

PubMed Central

Potgieter, Peter D.; Li, Yu-Ping; Barriere, Steven L.; Churukian, Allan; Kingsley, Jeff; Corey, G. Ralph

2012-01-01

TD-1792 is a first-in-class glycopeptide-cephalosporin heterodimer that exhibits bactericidal activity against Gram-positive pathogens. We conducted a randomized, double-blind, active-control, phase II trial in patients with complicated skin and skin structure infections caused by suspected or confirmed Gram-positive organisms. Patients 18 to 65 years old were randomized to receive 7 to 14 days of either TD-1792 (2 mg/kg of body weight intravenously [i.v.] every 24 h [q24h]) or vancomycin (1 g i.v. q12h, with dosage regimens adjusted per site-specific procedures). A total of 197 patients were randomized and received at least one dose of study medication. Rates of clinical success at the test-of-cure evaluation were similar in all analysis populations. Among 170 clinically evaluable patients, cure rates were 91.7% and 90.7% in the TD-1792 and vancomycin groups, respectively (95% confidence interval [CI] of −7.9 to 9.7 for the difference). In microbiologically evaluable patients with methicillin-resistant Staphylococcus aureus at baseline (n = 75), cure rates were 94.7% in the TD-1792 group and 91.9% in the vancomycin group. Microbiological eradication of Gram-positive pathogens (n = 126) was achieved in 93.7% and 92.1% of patients in the TD-1792 and vancomycin groups, respectively. Seven patients were discontinued from study medication due to an adverse event (AE): 2 and 5 in the TD-1792 and vancomycin groups, respectively. AEs were of similar types and severities between the two groups, other than pruritus, which was more common in patients who received vancomycin. No patients in the TD-1792 group experienced a serious AE. This study supports further clinical development of TD-1792 in patients with Gram-positive infection. PMID:22869571

75 FR 49023 - Proposed Collection; Comment Request for Form TD F 90-22.1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

... TD F 90-22.1 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for... Form TD F 90-22.1, Report of Foreign Bank and Financial Accounts. DATES: Written comments should be.... OMB Number: 1545-2038. Form Number: TD F 90-22.1. Abstract: This information is collected because of...

Earliest humans in Europe: The age of TD6 Gran Dolina, Atapuerca, Spain

USGS Publications Warehouse

Falgueres, Christophe; Bahain, J.-J.; Yokoyama, Y.; Arsuaga, J.L.; Bermudez de Castro, Jose Maria; Carbonell, E.; Bischoff, J.L.; Dolo, J.-M.

1999-01-01

Hominid remains found in 1994 from the stratified Gran Dolina karst-filling at the Atapuerca site in NE Spain were dated to somewhat greater than 780 ka based on palaeomagnetic measurements, making these the oldest known hominids in Europe (sensu stricto). We report new ESR and U-series results on teeth from four levels of the Gran Dolina deposit which confirm the palaeomagnetic evidence, and indicate that TD6 (from which the human remains have been recovered) dates to the end of the Early Pleistocene. The results for the other levels are consistent with estimates based mainly on microfaunal evidence, and suggest that TD8, TD10 and TD11 date to the Middle Pleistocene. (C) 1999 Academic Press.

Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of intrinsic brain activity.

PubMed

Zhang, Jiuquan; Wei, Luqing; Hu, Xiaofei; Xie, Bing; Zhang, Yanling; Wu, Guo-Rong; Wang, Jian

2015-01-01

Parkinson's disease (PD) is a surprisingly heterogeneous neurodegenerative disorder. It is well established that different subtypes of PD present with different clinical courses and prognoses. However, the neural mechanism underlying these disparate presentations is uncertain. Here we used resting-state fMRI (rs-fMRI) and the regional homogeneity (ReHo) method to determine neural activity patterns in the two main clinical subgroups of PD (akinetic-rigid and tremor-dominant). Compared with healthy controls, akinetic-rigid (AR) subjects had increased ReHo mainly in right amygdala, left putamen, bilateral angular gyrus, bilateral medial prefrontal cortex (MPFC), and decreased ReHo in left post cingulate gyrus/precuneus (PCC/PCu) and bilateral thalamus. In contrast, tremor-dominant (TD) patients showed higher ReHo mostly in bilateral angular gyrus, left PCC, cerebellum_crus1, and cerebellum_6, while ReHo was decreased in right putamen, primary sensory cortex (S1), vermis_3, and cerebellum_4_5. These results indicate that AR and TD subgroups both represent altered spontaneous neural activity in default-mode regions and striatum, and AR subjects exhibit more changed neural activity in the mesolimbic cortex (amygdala) but TD in the cerebellar regions. Of note, direct comparison of the two subgroups revealed a distinct ReHo pattern primarily located in the striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) loops. Overall, our findings highlight the involvement of default mode network (DMN) and STC circuit both in AR and TD subtypes, but also underscore the importance of integrating mesolimbic-striatal and CTC loops in understanding neural systems of akinesia and rigidity, as well as resting tremor in PD. This study provides improved understanding of the pathophysiological models of different subtypes of PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intentionally Designed Three-Phase Time Diary (TD) as a Multi-Pronged Practice

ERIC Educational Resources Information Center

Chen, Hsin-Yu; Yarnal, Careen

2017-01-01

Adopting qualitative approaches, this study highlights the value of integrating cognitive understanding with students' daily experiences through a time diary (TD) project. Using an innovative three-phase design, the TD effectively heightened self-awareness, promoted self-reflection, inspired the desire to change, and facilitated knowledge…

Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes.

PubMed

Al-Bachari, Sarah; Vidyasagar, Rishma; Emsley, Hedley Ca; Parkes, Laura M

2017-10-01

Neurovascular changes are likely to interact importantly with the neurodegenerative process in idiopathic Parkinson's disease (IPD). Markers of neurovascular status (NVS) include white matter lesion (WML) burden and arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). We investigated NVS in IPD, including an analysis of IPD clinical phenotypes, by comparison with two control groups, one with a history of clinical cerebrovascular disease (CVD) (control positive, CP) and one without CVD (control negative, CN). Fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant (TD), 24 postural instability and gait disorder (PIGD) and six intermediates), 18 CP (mean age 70.1 ± 8.0 years) and 34 CN subjects (mean age 67.4 ± 7.6 years) completed a 3T MRI scan protocol including T 2 -weighted fluid-attenuated inversion recovery (FLAIR) and ASL. IPD patients showed diffuse regions of significantly prolonged AAT, small regions of lower CBF and greater WML burden by comparison with CN subjects. TD patients showed lower WML volume by comparison with PIGD patients. These imaging data thus show altered NVS in IPD, with some evidence for IPD phenotype-specific differences.

75 FR 47893 - Proposed Collection; Comment Request for REG-111583-07, (T.D. 9405) (Final)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-09

...-111583-07, (T.D. 9405) (Final) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... comments concerning temporary and final regulations (REG-111583-07) (T.D. 9405), Employment Tax Adjustments... Adjustments. OMB Number: 1545-2097. Form Number: REG-111583-07 (T.D. 9405) (final). Abstract: This document...

Quality of life in Parkinson`s Disease

PubMed Central

Opara, JA; Brola, W; Leonardi, M; Błaszczyk, B

2012-01-01

In this review report, current possibilities of evaluation of quality of life in Parkinson’s disease have been critically presented. Health Related Quality of Life (-HRQoL) comprises a wide spectrum of consequences of the disease. Measurement of quality of life has become increasingly relevant as an outcome parameter, especially in long-term trials. Most of the available QoL instruments depend on patient self-reports. The data can be collected by written questionnaires. There are universal questionnaires of QoL – for many diseases and the specific ones – specially created for one disease. Among universal questionnaires, the Sickness Impact Profile (SIP) and the Short-Form Health Status Survey (SF-36) are the most popular in Parkinson’s disease. As for specific questionnaires: the Parkinson`s Disease Questionnaire (PDQ-39) and the Parkinson`s Disease Quality of Life Questionnaire (PDQL) have been described. PMID:23346238

Review of FD-TD numerical modeling of electromagnetic wave scattering and radar cross section

NASA Technical Reports Server (NTRS)

Taflove, Allen; Umashankar, Korada R.

1989-01-01

Applications of the finite-difference time-domain (FD-TD) method for numerical modeling of electromagnetic wave interactions with structures are reviewed, concentrating on scattering and radar cross section (RCS). A number of two- and three-dimensional examples of FD-TD modeling of scattering and penetration are provided. The objects modeled range in nature from simple geometric shapes to extremely complex aerospace and biological systems. Rigorous analytical or experimental validatons are provided for the canonical shapes, and it is shown that FD-TD predictive data for near fields and RCS are in excellent agreement with the benchmark data. It is concluded that with continuing advances in FD-TD modeling theory for target features relevant to the RCS problems and in vector and concurrent supercomputer technology, it is likely that FD-TD numerical modeling will occupy an important place in RCS technology in the 1990s and beyond.

An improved diffusion welding technique for TD-NiCr

NASA Technical Reports Server (NTRS)

Holko, K. H.

1973-01-01

An improved diffusion welding technique has been developed for TD-NiCr sheet. In the most preferred form, the improved technique consists of diffusion welding 320-grit sanded plus chemically polished surfaces of unrecrystallized TD-NiCr at 760 C under 140 MN/m2 pressure for 1hr followed by postheating at 1180 C for 2hr. Compared to previous work, this improved technique has the advantages of shorter welding time, lower welding temperature, lower welding pressure, and a simpler and more reproducible surface preparation procedure. Weldments were made that had parent-metal creep-rupture shear strength at 1100 C.

Parkinsonism in Spinocerebellar Ataxia

PubMed Central

Park, Hyeyoung; Kim, Han-Joon; Jeon, Beom S.

2015-01-01

Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive Parkinson disease (PD) like phenotype and atypical parkinsonism have been described especially in SCA2, SCA3, and SCA17 with geographic differences in prevalence. SCA2 is the most frequently reported subtype of SCA related to parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable in Asian populations especially in Korea. In addition, an unclear cutoff of the pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and pathologic features of parkinsonism in SCAs. PMID:25866756

Diagnostic accuracy of Parkinson's disease and atypical parkinsonism in nursing homes.

PubMed

Weerkamp, N J; Tissingh, G; Poels, P J E; Zuidema, S U; Munneke, M; Koopmans, R T C M; Bloem, B R

2014-11-01

Management of Parkinson's disease (PD) and atypical parkinsonism in nursing homes depends on a timely and accurate diagnosis. However, little is known about the diagnostic accuracy of these parkinsonian syndromes in nursing homes. We examined this issue in a large group of Dutch nursing home residents. Twelve large nursing home organizations in the Netherlands accounting for 100 nursing homes with a total population of 5480 residents participated. Residents with PD or atypical parkinsonism were identified according to their nursing home medical chart diagnosis. Additionally, local pharmacists provided a list of all residents using antiparkinson medication. We compared the admission diagnosis to a clinical diagnosis made in the study, based upon interview and detailed neurological examination by movement disorders experts. Diagnoses were based on accepted clinical criteria for PD and atypical parkinsonism. In the total population of 5480 residents, 258 had previously been diagnosed with a form of parkinsonism according to their medical record. In 53 of these residents (20.5%) we changed or rejected the diagnosis. Specifically, we found no parkinsonism in 22 of these 53 residents (8.5% of all patients with suspected parkinsonism). In the remaining 31 residents (12%), we established a new diagnosis within the parkinsonian spectrum. In a large population of Dutch nursing home residents, 20% of diagnoses within the parkinsonian spectrum were inaccurate. Almost 9% of residents had inadvertently received a diagnosis of parkinsonism. Better recognition of parkinsonism in nursing homes is important, because of the consequences for management and prognosis. Copyright © 2014. Published by Elsevier Ltd.

Normal CAG and CCG repeats in the Huntington`s disease genes of Parkinson`s disease patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinsztein, D.C.; Leggo, J.; Barton, D.E.

1995-04-24

The clinical features of Parkinson`s disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile-onset Huntington`s disease. Therefore, the CAG and CCG repeats in the Huntington`s disease gene were investigated in 45 Parkinson`s disease patients and compared to 40 control individuals. All of the Parkinson`s disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson`s disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington`s disease gene are not likely to contribute to the pathogenesis of Parkinson`s disease.more » 12 refs., 2 figs.« less

Parkinson disease

MedlinePlus

... this page: //medlineplus.gov/ency/article/000755.htm Parkinson disease To use the sharing features on this page, please enable JavaScript. Parkinson disease results from certain brain cells dying. These cells ...

Development and evaluation of the TD97 measles virus vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, K.; Morita, M.; Katoh, M.

1990-11-01

The TD97 strain vaccine virus was prepared from the Tanabe strain measles virus by low-temperature passages in primary cell cultures and ultraviolet (UV) mutagenesis. The TD97 strain exhibited the following characteristics: highly temperature sensitive, neither multiplying nor forming any plaques at 40 degrees C in Vero cells; genetically stable, maintaining high temperature sensitivity after ten successive passages in CE cells at 30 degrees C or 35 degrees C; and M proteins of this virus about 1 KD slower in mobility in SDS-PAGE than that of the Tanabe strain. The TD97 strain was further confirmed to be attenuated by an inoculationmore » test into primate brain. In field trials, 752 healthy children were inoculated with a live virus vaccine prepared with this strain, and the following results were obtained: the seroconversion rate was 97% (517/533), and the average HI antibody titer was 2(5.2). An antibody-increasing effect was also observed in children who were initially seropositive. In children who seroconverted, the rates of fever were 15.7% (55/351) for 37.5 degrees C or higher and 4.0% (14/351) for 39 degrees C or higher. The rash rate was 7.7% (27/351), and the incidence of local reaction was 5.4% (19/351). The TD97 strain is thus considered to be suitable in use for an attenuated measles vaccine.« less

Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters

PubMed Central

Zuo, Li-Jun; Piao, Ying-Shan; Li, Li-Xia; Yu, Shu-Yang; Guo, Peng; Hu, Yang; Lian, Teng-Hong; Wang, Rui-Dan; Yu, Qiu-Jin; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

2017-01-01

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF. PMID:28332604

There is no Parkinson disease.

PubMed

Weiner, William J

2008-06-01

The term Parkinson disease defines a specific clinical condition characterized by a typical history and characteristic signs. This review examines the historical evolution of the concept of Parkinson disease and how the misunderstanding of Parkinson disease may be hindering clinical research trials. It is proposed that this syndrome be called Parkinson diseases or parkinsonism type 1 through infinity.

Metallographic examination of TD-nickel base alloys. [thermal and chemical etching technique evaluation

NASA Technical Reports Server (NTRS)

Kane, R. D.; Petrovic, J. J.; Ebert, L. J.

1975-01-01

Techniques are evaluated for chemical, electrochemical, and thermal etching of thoria dispersed (TD) nickel alloys. An electrochemical etch is described which yielded good results only for large grain sizes of TD-nickel. Two types of thermal etches are assessed for TD-nickel: an oxidation etch and vacuum annealing of a polished specimen to produce an etch. It is shown that the first etch was somewhat dependent on sample orientation with respect to the processing direction, the second technique was not sensitive to specimen orientation or grain size, and neither method appear to alter the innate grain structure when the materials were fully annealed prior to etching. An electrochemical etch is described which was used to observe the microstructures in TD-NiCr, and a thermal-oxidation etch is shown to produce better detail of grain boundaries and to have excellent etching behavior over the entire range of grain sizes of the sample.

Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism.

PubMed

Tomiyama, Hiroyuki; Li, Yuanzhe; Yoshino, Hiroyo; Mizuno, Yoshikuni; Kubo, Shin-Ichiro; Toda, Tatsushi; Hattori, Nobutaka

2009-05-22

DJ-1 mutations cause autosomal recessive parkinsonism (ARP). Although some reports of DJ-1 mutations have been published, there is lack of information on the prevalence of these mutations in large-scale studies of both familial and sporadic parkinsonism. In this genetic screening study, we analyzed the distribution and frequency of DJ-1 mutations by direct nucleotide sequencing of coding exons and exon-intron boundaries of DJ-1, in 386 parkin-negative parkinsonism patients (371 index cases: 67 probands of autosomal recessive parkinsonism families, 90 probands of autosomal dominant parkinsonism families, 201 patients with sporadic parkinsonism, and 13 with unknown family histories) from 12 countries (Japan 283, China 27, Taiwan 22, Korea 22, Israel 16, Turkey 5, Philippines 2, Bulgaria 2, Greece 2, Tunisia 1, USA 2, Ukraine 1, unknown 1). None had causative mutation in DJ-1, suggesting DJ-1 mutation is very rare among patients with familial and sporadic parkinsonism from Asian countries and those with other ethnic background. This is in contrast to the higher frequencies and worldwide distribution of parkin- and PINK1-related parkinsonism in ARP and sporadic parkinsonism. Thus, after obtaining clinical information, screening for mutations in (1) parkin, (2) PINK1, (3) DJ-1, (4) ATP13A2 should be conducted in that order, in ARP and sporadic parkinsonism, based on their reported frequencies. In addition, haplotype analysis should be employed to check for homozygosity of 1p36, which harbors a cluster of causative genes for ARP such as DJ-1, PINK1 and ATP13A2 in ARP and sporadic parkinsonism, especially in parkinsonism with consanguinity.

One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease.

PubMed

Coenen, Volker Arnd; Rijntjes, Michel; Prokop, Thomas; Piroth, Tobias; Amtage, Florian; Urbach, Horst; Reinacher, Peter Christoph

2016-04-01

Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. Both patients showed immediate and sustained improvement of their tremor, bilaterally. The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research.

SSCC TD: A Serial and Simultaneous Configural-Cue Compound Stimuli Representation for Temporal Difference Learning

PubMed Central

Mondragón, Esther; Gray, Jonathan; Alonso, Eduardo; Bonardi, Charlotte; Jennings, Dómhnall J.

2014-01-01

This paper presents a novel representational framework for the Temporal Difference (TD) model of learning, which allows the computation of configural stimuli – cumulative compounds of stimuli that generate perceptual emergents known as configural cues. This Simultaneous and Serial Configural-cue Compound Stimuli Temporal Difference model (SSCC TD) can model both simultaneous and serial stimulus compounds, as well as compounds including the experimental context. This modification significantly broadens the range of phenomena which the TD paradigm can explain, and allows it to predict phenomena which traditional TD solutions cannot, particularly effects that depend on compound stimuli functioning as a whole, such as pattern learning and serial structural discriminations, and context-related effects. PMID:25054799

Inertial Navigation System for India's Reusable Launch Vehicle-Technology Demonstrator (RLV-TD HEX) Mission

NASA Astrophysics Data System (ADS)

Umadevi, P.; Navas, A.; Karuturi, Kesavabrahmaji; Shukkoor, A. Abdul; Kumar, J. Krishna; Sreekumar, Sreejith; Basim, A. Mohammed

2017-12-01

This work presents the configuration of Inertial Navigation System (INS) used in India's Reusable Launch Vehicle-Technology Demonstrator (RLV-TD) Program. In view of the specific features and requirements of the RLV-TD, specific improvements and modifications were required in the INS. A new system was designed, realised and qualified meeting the mission requirements of RLV-TD, at the same time taking advantage of the flight heritage attained in INS through various Launch vehicle Missions of the country. The new system has additional redundancy in acceleration channel, in-built inclinometer based bias update scheme for acceleration channels and sign conventions as employed in an aircraft. Data acquisition in micro cycle periodicity (10 ms) was incorporated which was required to provide rate and attitude information at higher sampling rate for ascent phase control. Provision was incorporated for acquisition of rate and acceleration data with high resolution for aerodynamic characterisation and parameter estimation. GPS aided navigation scheme was incorporated to meet the stringent accuracy requirements of the mission. Navigation system configuration for RLV-TD, specific features incorporated to meet the mission requirements, various tests carried out and performance during RLV-TD flight are highlighted.

An investigation of the magnetic field of Transient Disturbances (TD) at the Earth's orbit, and a determination of solar sources of TD from their characteristics at R = 1 AU

NASA Technical Reports Server (NTRS)

Fainshtein, V. .G.; Kaigorodov, A. P.

1995-01-01

We have investigated and intercompared the typical features of the magnetic field of two types of solar wind transient disturbances with shock waves: the shock wave is accompanied by a magnetic cloud (MC), and the shock wave is followed by a region with bidirectional solar wind electron heat flux (BEHF), with no MC present. In this case, a separate study was made of the field features in two typical TD structures: in the region of impact-compressed solar wind between the shock wave and MC or BEHF, as well as in MC and BEHF. The study has provided new results on the influence of the ambient SW upon the TD magnetic field and the relationship between fields in various TD structures. A new test for the existence of interplanetary magnetic field draping around MC and BEHF is proposed and verified. It is concluded that the magnetic field configuration around MC is more adequately consistent with the concept of magnetic line draping than is the case around BEHF Two methods are proposed to infer the location of solar sources of TD from their characteristics at R = 1 AU.

Shedding light on the Early Pleistocene of TD6 (Gran Dolina, Atapuerca, Spain): The technological sequence and occupational inferences

PubMed Central

2018-01-01

This paper aims to update the information available on the lithic assemblage from the entire sequence of TD6 now that the most recent excavations have been completed, and to explore possible changes in both occupational patterns and technological strategies evidenced in the unit. This is the first study to analyse the entire TD6 sequence, including subunits TD6.3 and TD6.1, which have never been studied, along with the better-known TD6.2 Homo antecessor-bearing subunit. We also present an analysis of several lithic refits found in TD6, as well as certain technical features that may help characterise the hominin occupations. The archaeo-palaeontological record from TD6 consists of 9,452 faunal remains, 443 coprolites, 1,046 lithic pieces, 170 hominin remains and 91 Celtis seeds. The characteristics of this record seem to indicate two main stages of occupation. In the oldest subunit, TD6.3, the lithic assemblage points to the light and limited hominin occupation of the cave, which does, however, grow over the course of the level. In contrast, the lithic assemblages from TD6.2 and TD6.1 are rich and varied, which may reflect Gran Dolina cave’s establishment as a landmark in the region. Despite the occupational differences between the lowermost subunit and the rest of the deposit, technologically the TD6 lithic assemblage is extremely homogeneous throughout. In addition, the composition and spatial distribution of the 12 groups of lithic refits found in unit TD6, as well as the in situ nature of the assemblage demonstrate the high degree of preservation at the site. This may help clarify the nature of the Early Pleistocene hominin occupations of TD6, and raise reasonable doubt about the latest interpretations that support the ex situ character of the assemblage as a whole. PMID:29370188

Shedding light on the Early Pleistocene of TD6 (Gran Dolina, Atapuerca, Spain): The technological sequence and occupational inferences.

PubMed

Mosquera, Marina; Ollé, Andreu; Rodríguez-Álvarez, Xose Pedro; Carbonell, Eudald

2018-01-01

This paper aims to update the information available on the lithic assemblage from the entire sequence of TD6 now that the most recent excavations have been completed, and to explore possible changes in both occupational patterns and technological strategies evidenced in the unit. This is the first study to analyse the entire TD6 sequence, including subunits TD6.3 and TD6.1, which have never been studied, along with the better-known TD6.2 Homo antecessor-bearing subunit. We also present an analysis of several lithic refits found in TD6, as well as certain technical features that may help characterise the hominin occupations. The archaeo-palaeontological record from TD6 consists of 9,452 faunal remains, 443 coprolites, 1,046 lithic pieces, 170 hominin remains and 91 Celtis seeds. The characteristics of this record seem to indicate two main stages of occupation. In the oldest subunit, TD6.3, the lithic assemblage points to the light and limited hominin occupation of the cave, which does, however, grow over the course of the level. In contrast, the lithic assemblages from TD6.2 and TD6.1 are rich and varied, which may reflect Gran Dolina cave's establishment as a landmark in the region. Despite the occupational differences between the lowermost subunit and the rest of the deposit, technologically the TD6 lithic assemblage is extremely homogeneous throughout. In addition, the composition and spatial distribution of the 12 groups of lithic refits found in unit TD6, as well as the in situ nature of the assemblage demonstrate the high degree of preservation at the site. This may help clarify the nature of the Early Pleistocene hominin occupations of TD6, and raise reasonable doubt about the latest interpretations that support the ex situ character of the assemblage as a whole.

Diabetes mellitus and Parkinson disease.

PubMed

Pagano, Gennaro; Polychronis, Sotirios; Wilson, Heather; Giordano, Beniamino; Ferrara, Nicola; Niccolini, Flavia; Politis, Marios

2018-05-08

To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease. We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline. The presence of diabetes mellitus was associated with higher motor scores ( p < 0.01), lower striatal dopamine transporter binding ( p < 0.05), and higher tau CSF levels ( p < 0.05) in patients with Parkinson disease. In patients with diabetes but without Parkinson disease, the presence of diabetes mellitus was associated with lower striatal dopamine transporter binding ( p < 0.05) and higher tau ( p < 0.05) and α-synuclein ( p < 0.05) CSF levels compared to healthy controls. At the Cox survival analysis in the population of patients with Parkinson disease, the presence of diabetes mellitus was associated with faster motor progression (hazard ratio = 4.521, 95% confidence interval = 1.468-13.926; p < 0.01) and cognitive decline (hazard ratio = 9.314, 95% confidence interval = 1.164-74.519; p < 0.05). Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype. © 2018 American Academy of Neurology.

Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes

PubMed Central

Pascale, Esterina; Di Battista, Maria Elena; Rubino, Alfonso; Purcaro, Carlo; Valente, Marcella; Fattapposta, Francesco; Ferraguti, Giampiero; Meco, Giuseppe

2016-01-01

The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ2 = 9.9; OR, 1.7; 95% CI, 1.2–2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ2 = 13.6; OR, 2.03; 95% CI, 1.4–3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3–6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype. PMID:27147968

Association of Parkinsonism or Parkinson Disease with Polypharmacy in the Year Preceding Diagnosis: A Nested Case-Control Study in South Korea.

PubMed

Park, Hae-Young; Park, Ji-Won; Sohn, Hyun Soon; Kwon, Jin-Won

2017-11-01

Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. From a South Korean national health insurance sample cohort database for 2002-2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28-1.55) and 2.17 (1.84-2.57) for parkinsonism and 2.87 (2.30-3.58) and 4.75 (3.39-6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson

Effects of TD-5108 on Gastrointestinal Transit and Bowel Function in Health and Pharmacokinetics in Health and Constipation

PubMed Central

Manini, Mhd Louai; Camilleri, Michael; Goldberg, Michael; Sweetser, Seth; McKinzie, Sanna; Burton, Duane; Wong, Shekman; Kitt, Michael M.; Li, Yu-Ping; Zinsmeister, Alan R.

2010-01-01

Background TD-5108 is a potent, selective high intrinsic activity serotonin 5-HT4 receptor agonist. Aim To assess effects of TD-5108 on gastrointestinal transit and compare its pharmacokinetics (PK) in healthy volunteers (HV) and chronic constipation (CC) patients. Methods 60 HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg TD-5108 (single and 6-day dosing). Primary endpoints were colonic transit (geometric center at 24 hours, GC24) and ascending colon emptying (ACE) T1/2 after first dose. Secondary endpoints included gastric emptying (GE) T1/2 and colonic filling at 6 h (CF6). Results Single dose TD-5108 significantly accelerated GC24, ACE T1/2, and CF6; 30 and 50°mg TD-5108 accelerated all 3 endpoints. With multiple doses, TD-5108 30 mg accelerated GC24, and overall accelerated GE T1/2 at 15–50 mg. PK studies showed dose proportionality in health, and no significant differences between health and chronic constipation with a 15 mg oral dose of TD-5108. Stimulation of bowel function after15 mg TD-5108 were similar in CC and controls. There were no serious adverse events; notable adverse were the predictable GI effects such as diarrhea or altered bowel movements. Conclusions TD-5108 significantly accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing. Further studies of its potential as a gastrointestinal and colonic prokinetic are warranted. PMID:19691492

Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

PubMed

Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

2017-12-01

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

TD-LTE Wireless Private Network QoS Transmission Protection

NASA Astrophysics Data System (ADS)

Zhang, Jianming; Cheng, Chao; Wu, Zanhong

With the commencement of construction of the smart grid, the demand power business for reliability and security continues to improve, the reliability transmission of power TD-LTE Wireless Private Network are more and more attention. For TD-LTE power private network, it can provide different QoS services according to the user's business type, to protect the reliable transmission of business. This article describes in detail the AF module of PCC in the EPC network, specifically introduces set up AF module station and QoS mechanisms in the EPS load, fully considers the business characteristics of the special power network, establishing a suitable architecture for mapping QoS parameters, ensuring the implementation of each QoS business. Through using radio bearer management, we can achieve the reliable transmission of each business on physical channel.

Parkinson disease - resources

MedlinePlus

Resources - Parkinson disease ... The following organizations are good resources for information on Parkinson disease : The Michael J. Fox Foundation -- www.michaeljfox.org National Institute of Neurological Disorders and Stroke -- www. ...

Diffusional creep and creep degradation in the dispersion-strengthened alloy TD-NiCr

NASA Technical Reports Server (NTRS)

Whittenberger, J. D.

1972-01-01

Dispersoid-free regions were observed in TD-NiCr (Ni-20Cr-2ThO2) after slow strain rate testing in air from 1145 to 1590 K. Formation of the dispersoid-free regions appears to be the result of diffusional creep. The net effect of this creep is the degradation of TD-NiCr to a duplex microstructure. Degradation is further enhanced by the formation of voids and integranular oxidation in the thoria-free regions. These regions apparently provided sites for void formation and oxide growth since the strength and oxidation resistance of Ni-20Cr is much less than Ni-20Cr-2ThO2. This localized oxidation does not appear to reduce the static load bearing capacity of TD-NiCr since long stress rupture lives were observed even with heavily oxidized microstructures. But this oxidation does significantly reduce the ductility and impact resistance of the material. Dispersoid-free bands and voids were also observed for two other dispersion strengthened alloys, TD-NiCrAl and IN-853. Thus, it appears that diffusional creep is charactertistic of dispersion-strengthened alloys and can play a major role in the creep degradation of these materials.

Enhanced efficacy of TD53, a novel algicidal agent, against the harmful algae via the liposomal delivery system.

PubMed

Han, Hyo-Kyung; Kim, Yeon-Mi; Lim, Soo-Jeong; Hong, Soon-Seok; Jung, Seul-Gi; Cho, Hoon; Lee, Wonjae; Jin, Eonseon

2011-02-28

The present study aimed to design the liposomal delivery system for TD53, a novel algicial drug in order to improve the delivery properties of TD53 and evaluate its algicidal effects as well as selectivity against harmful and non-harmful algae. Liposomes of TD53 were prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) by a lyophilization, resulting in relatively small size vesicles (234±38nm) and narrow size distribution (PI=0.130±0.027). The drug leakage from the liposome was negligible in the F/2 media (<2% during 96h incubation). Subsequently algicidal activity of liposomal TD53 against harmful and nonharmful algae was evaluated at various concentrations. The IC(50) values of TD53 in liposome against harmful algae such as Chattonella marina, Heterosigma akashiwo and Cocholodinium polykrikoides were 2.675, 2.029, and 0.480μM, respectively, and were reduced by approximately 50% compared to those obtained from non-liposomal TD53. In contrast, the algicidal effect of liposomal TD53 was insignificant against non-harmful algae including Navicula pelliculosa, Nannochloropsis oculata and Phaeodactylum EPV. Those results suggested that liposomal delivery systems might be effective to enhance the efficacy of TD53 while maintaining the selectivity to harmful algal species. Copyright © 2010 Elsevier B.V. All rights reserved.

Optical properties of alkali halide crystals from all-electron hybrid TD-DFT calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, R., E-mail: ross.webster07@imperial.ac.uk; Harrison, N. M.; Bernasconi, L.

2015-06-07

We present a study of the electronic and optical properties of a series of alkali halide crystals AX, with A = Li, Na, K, Rb and X = F, Cl, Br based on a recent implementation of hybrid-exchange time-dependent density functional theory (TD-DFT) (TD-B3LYP) in the all-electron Gaussian basis set code CRYSTAL. We examine, in particular, the impact of basis set size and quality on the prediction of the optical gap and exciton binding energy. The formation of bound excitons by photoexcitation is observed in all the studied systems and this is shown to be correlated to specific features ofmore » the Hartree-Fock exchange component of the TD-DFT response kernel. All computed optical gaps and exciton binding energies are however markedly below estimated experimental and, where available, 2-particle Green’s function (GW-Bethe-Salpeter equation, GW-BSE) values. We attribute this reduced exciton binding to the incorrect asymptotics of the B3LYP exchange correlation ground state functional and of the TD-B3LYP response kernel, which lead to a large underestimation of the Coulomb interaction between the excited electron and hole wavefunctions. Considering LiF as an example, we correlate the asymptotic behaviour of the TD-B3LYP kernel to the fraction of Fock exchange admixed in the ground state functional c{sub HF} and show that there exists one value of c{sub HF} (∼0.32) that reproduces at least semi-quantitatively the optical gap of this material.« less

Parkinson's Disease Videos

MedlinePlus Videos and Cool Tools

... Parkinson's Disease Expert Briefings: Getting Around: Transportation and Travel with PD Expert Briefings: Sleep and Parkinson's Nurse: ... Psychosis Why We Walk at Moving Day CareMAP: Travel and Transportation: Part 2 Interview with Nathan Slewett ...

No allelic association between Parkinson`s disease and dopamine D2, D3, and D4 receptor gene polymorphisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanko, S.; Hattori, M.; Dai, X.Y.

1994-12-15

Parkinson`s disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson`s disease. Genetic association studies between Parkinson`s disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson`s disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson`s disease ismore » associated with the dopamine receptor polymorphisms examined. 35 refs., 2 tabs.« less

PDON: Parkinson's disease ontology for representation and modeling of the Parkinson's disease knowledge domain.

PubMed

Younesi, Erfan; Malhotra, Ashutosh; Gündel, Michaela; Scordis, Phil; Kodamullil, Alpha Tom; Page, Matt; Müller, Bernd; Springstubbe, Stephan; Wüllner, Ullrich; Scheller, Dieter; Hofmann-Apitius, Martin

2015-09-22

Despite the unprecedented and increasing amount of data, relatively little progress has been made in molecular characterization of mechanisms underlying Parkinson's disease. In the area of Parkinson's research, there is a pressing need to integrate various pieces of information into a meaningful context of presumed disease mechanism(s). Disease ontologies provide a novel means for organizing, integrating, and standardizing the knowledge domains specific to disease in a compact, formalized and computer-readable form and serve as a reference for knowledge exchange or systems modeling of disease mechanism. The Parkinson's disease ontology was built according to the life cycle of ontology building. Structural, functional, and expert evaluation of the ontology was performed to ensure the quality and usability of the ontology. A novelty metric has been introduced to measure the gain of new knowledge using the ontology. Finally, a cause-and-effect model was built around PINK1 and two gene expression studies from the Gene Expression Omnibus database were re-annotated to demonstrate the usability of the ontology. The Parkinson's disease ontology with a subclass-based taxonomic hierarchy covers the broad spectrum of major biomedical concepts from molecular to clinical features of the disease, and also reflects different views on disease features held by molecular biologists, clinicians and drug developers. The current version of the ontology contains 632 concepts, which are organized under nine views. The structural evaluation showed the balanced dispersion of concept classes throughout the ontology. The functional evaluation demonstrated that the ontology-driven literature search could gain novel knowledge not present in the reference Parkinson's knowledge map. The ontology was able to answer specific questions related to Parkinson's when evaluated by experts. Finally, the added value of the Parkinson's disease ontology is demonstrated by ontology-driven modeling of PINK1

Genetics Home Reference: Parkinson disease

MedlinePlus

... Email Facebook Twitter Home Health Conditions Parkinson disease Parkinson disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Parkinson disease is a progressive disorder of the nervous system. ...

Parkinson's Disease: Diagnosis and Treatment

MedlinePlus

... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease: Diagnosis and Treatment Past Issues / Winter 2014 Table of Contents Medications for Parkinson's disease can help many patients live productive lives and ...

Laughter Yoga, Adults Living With Parkinson׳s Disease, and Caregivers: A Pilot Study.

PubMed

DeCaro, Debra Swedberg; Constantine Brown, Jodi L

2016-01-01

This study explored outcomes of Laughter Yoga in adults with Parkinson׳s disease (PD) and their caregivers. Laughter has been shown to generally improve mood in physically healthy adults, and specifically in adults with heart disease or cancer, but little research exists regarding the impact of laughter in adults with Parkinson׳s disease. Low mood is frequently a co-morbid condition for adults with Parkinson׳s disease, and can negatively affect their caregivers. Pre-experimental (O1 × O2) pretest-posttest design. Data collection occurred at six unique PD support groups in Southern California. Participants (N = 85) comprised a convenience sample of adults diagnosed with Parkinson׳s disease (n = 47) and accompanying caregivers (n = 38). Subjects participated in a 45-min Laughter Yoga (LY) session conducted by a Certified Laughter Yoga Teacher. This study utilized the Laughter Yoga "How Do You Feel?" (HDYF) form. The form consists of a series of 10 scales labeled "well-being" measures including enthusiasm, energy level, mood, optimism, stress level, level of friendship with group members, level of awareness about breathing, level of muscle relaxation, level of mental relaxation, and ability to laugh without a reason. Paired sample t-tests reveal statistically significant improvements in well-being for adults with PD and their caregivers after attending an LY session. Therapists and other clinicians should consider utilizing this unique technique with adults with PD to address co-morbid low-mood conditions and include caregivers in the LY sessions for support and their own benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

PubMed

Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X

2017-05-01

Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

Design and qualification of the SEU/TD Radiation Monitor chip

NASA Technical Reports Server (NTRS)

Buehler, Martin G.; Blaes, Brent R.; Soli, George A.; Zamani, Nasser; Hicks, Kenneth A.

1992-01-01

This report describes the design, fabrication, and testing of the Single-Event Upset/Total Dose (SEU/TD) Radiation Monitor chip. The Radiation Monitor is scheduled to fly on the Mid-Course Space Experiment Satellite (MSX). The Radiation Monitor chip consists of a custom-designed 4-bit SRAM for heavy ion detection and three MOSFET's for monitoring total dose. In addition the Radiation Monitor chip was tested along with three diagnostic chips: the processor monitor and the reliability and fault chips. These chips revealed the quality of the CMOS fabrication process. The SEU/TD Radiation Monitor chip had an initial functional yield of 94.6 percent. Forty-three (43) SEU SRAM's and 14 Total Dose MOSFET's passed the hermeticity and final electrical tests and were delivered to LL.

An electron microscopy examination of primary recrystallization in TD-nickel.

NASA Technical Reports Server (NTRS)

Petrovic, J. J.; Ebert, L. J.

1972-01-01

Primary recrystallization in TD-nickel 1 in. bar has previously been regarded as the process by which the initial fine grain structure is converted to a coarse grain size (increases in grain size by 500 times) under suitable deformation and annealing conditions. This process is dependent on deformation mode. While it occurs readily after rolling transverse to the bar axis and annealing (800 C), it is completely inhibited by longitudinal rolling and swaging deformations, even for very high (1320 C) annealing temperatures. A transmission electron microscopy examination of deformation and annealing substructures indicates that primary recrystallization in TD-nickel 1 in. bar actually occurs on the sub-light optical level, to produce a grain structure similar in size to the initial fine grained state.

Development of forming and joining technology for TD-NiCr sheet

NASA Technical Reports Server (NTRS)

Torgerson, R. T.

1973-01-01

Forming joining techniques and properties data were developed for thin-gage TD-NiCr sheet in the recrystallized and unrecrystallized conditions. Theoretical and actual forming limit data are presented for several gages of each type of material for five forming processes: brake forming, corrugation forming, joggling, dimpling and beading. Recrystallized sheet can be best formed at room temperature, but unrecrystallized sheet requires forming at elevated temperature. Formability is satisfactory with most processes for the longitudinal orientation but poor for the transverse orientation. Dimpling techniques require further development for both material conditions. Data on joining techniques and joint properties are presented for four joining processes: resistance seam welding (solid-state), resistance spot welding (solid-state), resistance spot welding (fusion) and brazing. Resistance seam welded (solid-state) joints with 5t overlap were stronger than parent material for both material conditions when tested in tensile-shear and stress-rupture. Brazing studies resulted in development of NASA 18 braze alloy (Ni-16Cr-15Mo-8Al-4Si) with several properties superior to baseline TD-6 braze alloy, including lower brazing temperture, reduced reaction with Td-Ni-Cr, and higher stress-rupture properties.

Different patterns of spontaneous brain activity between tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease: a resting-state fMRI study.

PubMed

Chen, Hui-Min; Wang, Zhi-Jiang; Fang, Jin-Ping; Gao, Li-Yan; Ma, Ling-Yan; Wu, Tao; Hou, Ya-Nan; Zhang, Jia-Rong; Feng, Tao

2015-10-01

Postural instability/gait difficulty (PIGD) and tremor-dominant (TD) subtypes of Parkinson's disease (PD) show different clinical manifestations; however, their underlying neural substrates remain incompletely understood. This study aimed at investigating the subtype-specific patterns of spontaneous brain activity in PD. Thirty-one patients with PD (12 TD/19 PIGD) and 22 healthy gender- and age-matched controls were recruited. Resting-state functional magnetic resonance imaging data were collected, and amplitude of low-frequency fluctuations (ALFF) was measured. Voxelwise one-way analysis of covariance and post hoc analyses of ALFF were performed among the three groups, with age and gender as covariates (levodopa daily dosage and gray matter volume as additional covariates for validation analysis). Correlations of clinical variables (e.g., disease duration and PIGD/tremor subscale score) with ALFF values were examined. Compared with controls, patients with TD exhibited higher ALFF in the right cerebellar posterior lobe and patients with PIGD exhibited lower ALFF in the bilateral putamen and cerebellar posterior lobe, and higher values primarily in several cortical areas including the inferior and superior temporal gyrus, superior frontal, and parietal gyrus. Compared with patients with PIGD, patients with TD had higher ALFF in the bilateral putamen and the cerebellar posterior lobe, as well as lower ALFF in the bilateral temporal gyrus and the left superior parietal lobule. In all patients, ALFF in the bilateral cerebellar posterior lobe positively correlated with tremor score and ALFF in the bilateral putamen negatively correlated with PIGD score. Different patterns of spontaneous neural activity in the cerebellum and putamen may underlie the neural substrate of PD motor subtypes. © 2015 John Wiley & Sons Ltd.

Hitler's parkinsonism.

PubMed

Boettcher, Lillian B; Bonney, Phillip A; Smitherman, Adam D; Sughrue, Michael E

2015-07-01

Of the multitude of medical and psychiatric conditions ascribed to Hitler both in his lifetime and since his suicide in April 1945, few are more substantiated than parkinsonism. While the timeline of the development of this condition, as well as its etiology, are debated, there is clear evidence for classic manifestations of the disease, most prominently a resting tremor but also stooped posture, bradykinesia, micrographia, and masked facial expressions, with progression steadily seen over his final years. Though ultimately speculation, some have suggested that Hitler suffered from progressive cognitive and mood disturbances, possibly due to parkinsonism, that affected the course of events in the war. Here, the authors discuss Hitler's parkinsonism in the context of the Third Reich and its eventual destruction, maintaining that ultimately his disease had little effect on the end result.

Hereditary Parkinson s Disease Natural History Protocol

ClinicalTrials.gov

2018-03-27

Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1

Can loss of the swallow tail sign help distinguish between Parkinson Disease and the Parkinson-Plus syndromes?

PubMed

Oustwani, Christopher Sami; Korutz, Alexander William; Lester, Malisa Siri; Kianirad, Yasaman; Simuni, Tanya; Hijaz, Tarek Aref

To determine if loss of the swallow tail sign (STS) can distinguish Parkinson Disease (PD) from the Parkinson-Plus syndromes. Twenty-five patients with PD, 21 with Parkinson-Plus syndromes, and 14 control patients were included. Presence of the STS was assessed. The STS was present in 79% of controls, statistically greater than the PD/Parkinson-Plus patients. There was no difference in the presence of the STS between the PD/Parkinson-Plus subgroups or when scanning at 1.5 T or 3 T. Loss of the STS could not distinguish between PD and Parkinson-Plus patients. The STS can be identified at both 1.5 T and 3 T. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers.

PubMed

Strafella, Antonio P; Bohnen, Nicolaas I; Perlmutter, Joel S; Eidelberg, David; Pavese, Nicola; Van Eimeren, Thilo; Piccini, Paola; Politis, Marios; Thobois, Stephane; Ceravolo, Roberto; Higuchi, Makoto; Kaasinen, Valtteri; Masellis, Mario; Peralta, M Cecilia; Obeso, Ignacio; Pineda-Pardo, Jose Ángel; Cilia, Roberto; Ballanger, Benedicte; Niethammer, Martin; Stoessl, Jon A

2017-02-01

Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

BK/TD models for analyzing in vitro impedance data on cytotoxicity.

PubMed

Teng, S; Barcellini-Couget, S; Beaudouin, R; Brochot, C; Desousa, G; Rahmani, R; Pery, A R R

2015-06-01

The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48 h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Prevalence of parkinsonism and Parkinson's disease in the Arosa Island (Spain): a community-based door-to-door survey.

PubMed

Seijo-Martinez, M; Castro del Rio, M; Rodríguez Alvarez, J; Suarez Prado, R; Torres Salgado, E; Paz Esquete, J; Sobrido, M J

2011-05-15

There are scarce epidemiological data on parkinsonism in Spain. Since the Arosa Island community (Northwestern Spain) has been for centuries relatively isolated, it represents a potentially useful setting to undercover genetic factors with a founder effect, as well as local environmental influences. We performed a one-stage door-to-door survey in the Arosa Island in 2004 to determine the prevalence of parkinsonism and Parkinson's disease (PD) in the population aged 65 years or over. Out of 41 individuals detected with parkinsonism, 15 were diagnosed with PD (36.6%), 13 with drug induced parkinsonism (31.7%), seven with vascular parkinsonism (17.1%), four patients had parkinsonism with associated features (9.8%) and two had unspecified parkinsonism (4.9%). We obtained a crude prevalence rate of parkinsonism of 5.44% (adjusted rate: 4.73%) and a crude prevalence rate of PD of 1.99% (adjusted rate 1.7%); both prevalence rates increased with advancing age. The prevalence rate for parkinsonism was higher than that in similar populations of Spain and other European countries while that for PD was in the range obtained from these populations. Among PD cases, 26.7% (n=4) were undiagnosed before the survey. Most cases of drug-induced parkinsonism were secondary to neuroleptics and had not been previously diagnosed. The relatively high proportion of undiagnosed drug-induced parkinsonisms and PD is surprising in a public health system which is free and universal. The lack of excess of late-onset PD among Arosans does not support the existence of specific genetic or environmental factors contributing to PD in this particular geographical area. Copyright © 2011 Elsevier B.V. All rights reserved.

A mixed-methods study into ballet for people living with Parkinson's1

PubMed Central

Houston, Sara; McGill, Ashley

2012-01-01

Background: Parkinson's is a neurological disease that is physically debilitating and can be socially isolating. Dance is growing in popularity for people with Parkinson's and claims have been made for its benefits. The paper details a mixed-methods study that examined a 12-week dance project for people with Parkinson's, led by English National Ballet. Methods: The effects on balance, stability and posture were measured through the Fullerton Advanced Balance Scale and a plumb-line analysis. The value of participation and movement quality were interpreted through ethnographic methods, grounded theory and Effort analysis. Results: Triangulation of results indicates that people were highly motivated, with 100% adherence, and valued the classes as an important part of their lives. Additionally, results indicated an improvement in balance and stability, although not in posture. Conclusions: Dancing may offer benefit to people with Parkinson's through its intellectual, artistic, social and physical aspects. The paper suggests that a range of research methods is fundamental to capture the importance of multifaceted activity, such as dance, to those with Parkinson's. PMID:23805165

Safety and immunogenicity of a single intramuscular dose of a tetanus-diphtheria toxoid (Td) vaccine (BR-TD-1001) in healthy Korean adult subjects.

PubMed

Hong, Taegon; Chung, Yong-Ju; Kim, Tae-Yeon; Kim, Ik-Hwan; Choe, Yong-Kyung; Lee, Jongtae; Jeon, Sangil; Han, Seunghoon; Yim, Dong-Seok

2015-01-01

BR-TD-1001 was developed as a booster for the immunity maintenance of diphtheria and tetanus. The aim of this study was to evaluate the safety and immunogenicity of BR-TD-1001 (test vaccine) in comparison with placebo and an active comparator in healthy Korean adults. A randomized, double-blind, placebo-controlled, active comparator, phase I clinical trial was conducted. Fifty subjects were randomly assigned to one of 3 treatment groups in a ratio of 2:2:1, and were administered a single intramuscular dose of test vaccine, active comparator, or placebo, respectively. All subjects were monitored for 4 weeks after injection. The antibody titers of the patients 2 and 4 weeks after vaccination were compared with the baseline. The frequencies of all adverse events including adverse drug reactions in the test group were not statistically different from those of the other treatment groups (P = 0.4974, 0.3061). No serious adverse event occurred, and no subject was withdrawn from the study for safety. The seroprotection rates against both tetanus and diphtheria at 4 weeks after vaccination were over 0.95. For anti-tetanus antibody, the geometric mean titer in the test group was significantly higher than those of the other groups (P = 0.0364, 0.0033). The geometric mean titer of anti-diphtheria antibody in the test group was significantly higher than the value of the placebo (P = 0.0347) while it was not for the value of the active comparator (P = 0.8484). In conclusion, BR-TD-1001 was safe, well-tolerated, and showed sufficient immunogenicity as a booster for diphtheria and tetanus.

Adolf Hitler had post-encephalitic Parkinsonism.

PubMed

Lieberman, A

1996-04-01

Adolf Hitler had Parkinson symptoms in 1934, at age 45 years. He may have had transient symptoms in 1923, at age 34 years. Young-onset parkinsonism, during the 1920s, favored a diagnosis of post-encephalitic rather than idiopathic parkinsonism. Hitler had oculogyric crises, phenomena only associated with post-encephalitic parkinsonism. In addition, he had dystonic facial spasms, palilalia and a sleep disorder, phenomena more likely to be associated with post-encephalitic than idiopathic parkinsonism. In November 1918, at age 29 years, Hitler may have had von Economo's encephalitis, while he was a patient in a hospital, recovering from poison gas. This paper looks at the possible relationship of von Economo's encephalitis to Hitler's asocial behavior; his obsessions and compulsions, his cruelty and rages. The influence of Hitler's parkinsonism on his conduct during World War II is discussed.

Td Vaccine (Tetanus and Diphtheria): What You Need to Know

MedlinePlus

... protect adolescents and adults from both of these diseases. Both tetanus and diphtheria are infections caused by bacteria. Diphtheria ... cases of diphtheria and hundreds of cases of tetanus were reported in the United ... both diseases have dropped by about 99%. 2 Td vaccine ...

Electroconvulsive Therapy Intervention for Parkinson's Disease.

PubMed

Narang, Puneet; Glowacki, Anna; Lippmann, Steven

2015-01-01

Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

Parkinson's Disease, Diabetes and Cognitive Impairment.

PubMed

Ashraghi, Mohammad R; Pagano, Gennaro; Polychronis, Sotirios; Niccolini, Flavia; Politis, Marios

2016-01-01

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Presymptomatic detection of Parkinson's disease.

PubMed

Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

Electronic spectroscopy of HRe(CO) 5: a CASSCF/CASPT2 and TD-DFT study

NASA Astrophysics Data System (ADS)

Bossert, J.; Ben Amor, N.; Strich, A.; Daniel, C.

2001-07-01

The low-lying excited states of HRe(CO) 5 have been calculated at the CASSCF/CASPT2 and TD-DFT level of theory using relativistic effective core potentials (ECP) or ab initio model potentials (AIMP). The theoretical absorption spectrum is compared to the experimental one. Despite the similarity between the experimental absorption spectra of HMn(CO) 5 and HRe(CO) 5 in the UV/visible energy domain it is shown that the assignment differs significantly between the two molecules. The low-lying excited states of HRe(CO) 5 correspond to 5d→π *CO excitations whereas the spectrum of HMn(CO) 5 consists mainly of 3d→3d and 3d→ σ*Mn-H excitations. If the CASPT2 and TD-DFT results are quite comparable for the lowest excited states, the upper part assignment is more problematic with the TD-DFT method.

[Sexual delinquency and Parkinson's disease].

PubMed

Berger, Ch; Mehrhoff, F W; Beier, K M; Meinck, H-M

2003-04-01

The risk of aberrant sexual behaviour such as hypersexuality, exhibitionism, or pederasty may be underestimated in Parkinson's disease and its therapy with high-dosage L-dopa or dopamine agonists. We describe two legal cases which are representative of the forensic assessment of these side effects. The first case brought to court was a 45-year-old man suffering for 20 years from Parkinson's disease who developed hypersexuality and exhibitionism under high-dose therapy with ropinirol. The second patient, a 57-year-old man with an 11-year history of Parkinson's disease, developed increased libido and pederasty under therapy with L-dopa and bromocriptine. We discuss the present literature concerning hypersexuality and sexually deviant behaviour in Parkinson's disease and dopaminergic therapy in the German legal context. Doctors treating Parkinson patients should be aware of increased sexual impulses or reduced behavioural control and ask specifically about them during anamnesis, and counteractive therapeutic strategies should be considered to prevent the occurrence of illegal sexually aberrant behavioural disorders.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

PubMed

Vasta, Rosario; Nicoletti, Alessandra; Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

2017-01-01

Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40-13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Final Phase Flight Performance and Touchdown Time Assessment of TDV in RLV-TD HEX-01 Mission

NASA Astrophysics Data System (ADS)

Yadav, Sandeep; Jayakumar, M.; Nizin, Aziya; Kesavabrahmaji, K.; Shyam Mohan, N.

2017-12-01

RLV-TD HEX-01 mission was configured as a precursor flight to actual two stages to orbit vehicle. In this mission RLV-TD was designed as a two stage vehicle for demonstrating the hypersonic flight of a winged body vehicle at Mach No. 5. One of the main objectives of this mission was to generate data for better understanding of new technologies required to design the future vehicle. In this mission, the RLV-TD vehicle was heavily instrumented to get data related to performance of different subsystems. As per the mission design, RLV-TD will land in sea after flight duration of 700 s and travelling a distance of nearly 500 km in Bay of Bengal from the launch site for a nominal trajectory. The visibility studies for telemetry data of vehicle for the nominal and off nominal trajectories were carried out. Based on that, three ground stations were proposed for the telemetry data reception (including one in sea). Even with this scheme it was seen that during the final phase of the flight there will not be any ground station visible to the flight due to low elevation. To have the mission critical data during final phase of the flight, telemetry through INSAT scheme was introduced. During the end of the mission RLV-TD will be landing in the sea on a hypothetical runway. To know the exact time of touchdown for the flight in sea, there was no direct measurement available. Simultaneously there were all chances of losing ground station visibility just before touchdown, making it difficult to assess flight performance during that phase. In this work, telemetry and instrumentation scheme of RLV-TD HEX-01 mission is discussed with an objective to determine the flight performance during the final phase. Further, using various flight sensor data the touchdown time of TDV is assessed for this mission.

Parkinson disease.

PubMed

Poewe, Werner; Seppi, Klaus; Tanner, Caroline M; Halliday, Glenda M; Brundin, Patrik; Volkmann, Jens; Schrag, Anette-Eleonore; Lang, Anthony E

2017-03-23

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

Large-Scale Wearable Sensor Deployment in Parkinson's Patients: The Parkinson@Home Study Protocol.

PubMed

Silva de Lima, Ana Lígia; Hahn, Tim; de Vries, Nienke M; Cohen, Eli; Bataille, Lauren; Little, Max A; Baldus, Heribert; Bloem, Bastiaan R; Faber, Marjan J

2016-08-26

Long-term management of Parkinson's disease does not reach its full potential because we lack knowledge about individual variations in clinical presentation and disease progression. Continuous and longitudinal assessments in real-life (ie, within the patients' own home environment) might fill this knowledge gap. The primary aim of the Parkinson@Home study is to evaluate the feasibility and compliance of using multiple wearable sensors to collect clinically relevant data. Our second aim is to address the usability of these data for answering clinical research questions. Finally, we aim to build a database for future validation of novel algorithms applied to sensor-derived data from Parkinson's patients during daily functioning. The Parkinson@Home study is a two-phase observational study involving 1000 Parkinson's patients and 250 physiotherapists. Disease status is assessed using a short version of the Parkinson's Progression Markers Initiative protocol, performed by certified physiotherapists. Additionally, participants will wear a set of sensors (smartwatch, smartphone, and fall detector), and use these together with a customized smartphone app (Fox Insight), 24/7 for 3 months. The sensors embedded within the smartwatch and fall detector may be used to estimate physical activity, tremor, sleep quality, and falls. Medication intake and fall incidents will be measured via patients' self-reports in the smartphone app. Phase one will address the feasibility of the study protocol. In phase two, mathematicians will distill relevant summary statistics from the raw sensor signals, which will be compared against the clinical outcomes. Recruitment of 300 participants for phase one was concluded in March, 2016, and the follow-up period will end in June, 2016. Phase two will include the remaining participants, and will commence in September, 2016. The Parkinson@Home study is expected to generate new insights into the feasibility of integrating self-collected information from

Modeling Excited States in TiO2 Nanoparticles: On the Accuracy of a TD-DFT Based Description

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berardo, Enrico; Hu, Hanshi; Shevlin, S. A.

2014-03-11

We have investigated the suitability of Time-Dependent Density Functional Theory (TD-DFT) to describe vertical low-energy excitations in naked and hydrated titanium dioxide nanoparticles through a comparison with results from Equation-of-Motion Coupled Cluster (EOM-CC) quantum chemistry methods. We demonstrate that for most TiO2 nanoparticles TD-DFT calculations with commonly used exchange-correlation (XC-)potentials (e.g. B3LYP) and EOM-CC methods give qualitatively similar results. Importantly, however, we also show that for an important subset of structures, TD-DFT gives qualitatively different results depending upon the XC-potential used and that in this case only TD-CAM-B3LYP and TD-BHLYP calculations yield results that are consistent with those obtained usingmore » EOM-CC theory. Moreover, we demonstrate that the discrepancies for such structures arise from a particular combination of defects, excitations involving which are charge-transfer excitations and hence are poorly described by XC-potentials that contain no or low fractions of Hartree-Fock like exchange. Finally, we discuss that such defects are readily healed in the presence of ubiquitously present water and that as a result the description of vertical low-energy excitations for hydrated TiO2 nanoparticles is hence non-problematic.« less

Dysphagia and sialorrhea: the relationship to Parkinson's disease.

PubMed

Nicaretta, Denise Hack; Rosso, Ana Lucia; Mattos, James Pitágoras de; Maliska, Carmelindo; Costa, Milton M B

2013-01-01

Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

Atmospheric Pressure-Thermal Desorption (AP-TD)/Electrospray Ionization-Mass Spectrometry for the Rapid Analysis of Bacillus Spores

USDA-ARS?s Scientific Manuscript database

A technique is described where an atmospheric pressure-thermal desorption (AP-TD) device and electrospray ionization (ESI)-mass spectrometry are coupled and used for the rapid analysis of Bacillus spores in complex matrices. The resulting AP-TD/ESI-MS technique combines the generation of volatile co...

Cardiac abnormalities in Parkinson's disease and Parkinsonism.

PubMed

Scorza, Fulvio A; Fiorini, Ana C; Scorza, Carla A; Finsterer, Josef

2018-07-01

Though there is increasing evidence for primary cardiac disease in Parkinson's disease (PD) and Parkinsonism (PS), this evidence is hardly included in the general management of these patients. Literature review. PD is one of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that PD is accompanied by high rates of premature death compared with the general population. In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS. Cardiac involvement in PD/PS includes cardiac autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmias, conduction defects, and sudden cardiac death (SCD), and sudden unexpected death in Parkinson's disease (SUDPAR). Cardiac abnormalities found in PD/PS are manifold but the most prominent is cardiac autonomic dysfunction. The frequency of coronary heart disease in PD is a matter of debate. Only rarely reported in PD/PS are cardiomyopathies, arrhythmias, and sudden cardiac death, and SUDPAR. It is particularly recommended that PD/PS patients are more intensively investigated cardiologically as soon as the diagnosis is established. Early recognition of cardiac involvement is important for preventing SCD and SUDPAR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Michael J. Fox: Spurring Research on Parkinson's

MedlinePlus

... on. Feature: Parkinson's Disease Michael J. Fox: Spurring Research on Parkinson's Past Issues / Winter 2014 Table of ... founded the Michael J. Fox Foundation for Parkinson's Research in the year 2000. Photo courtesy of Shutterstock " ...

TdKT, a new killer toxin produced by Torulaspora delbrueckii effective against wine spoilage yeasts.

PubMed

Villalba, María Leticia; Susana Sáez, Julieta; Del Monaco, Silvana; Lopes, Christian Ariel; Sangorrín, Marcela Paula

2016-01-18

Microbiological spoilage is a major concern throughout the wine industry, and control tools are limited. This paper addresses the identification and partial characterization of a new killer toxin from Torulaspora delbrueckii with potential biocontrol activity of Brettanomyces bruxellensis, Pichia guilliermondii, Pichia manshurica and Pichia membranifaciens wine spoilage. A panel of 18 different wine strains of T. delbrueckii killer yeasts was analysed, and the strain T. delbrueckii NPCC 1033 (TdKT producer) showed a significant inhibitory effect on the growth of all different spoilage yeasts evaluated. The TdKT toxin was then subjected to a partial biochemical characterization. Its estimated molecular weight was N30 kDa and it showed glucanase and chitinase enzymatic activities. The killer activity was stable between pH 4.2 and 4.8 and inactivated at temperature above 40 °C. Pustulan and chitin — but not other cell wall polysaccharides — prevented sensitive yeast cells from being killed by TdKT, suggesting that those may be the first toxin targets in the cell wall. TdKT provoked an increase in necrosis cell death after 3 h treatment and apoptotic cell death after 24 h showing time dependence in its mechanisms of action. Killer toxin extracts were active at oenological conditions, confirming their potential use as a biocontrol tool in winemaking.

Treatment of early Parkinson's disease.

PubMed

Pahwa, Rajesh; Lyons, Kelly E

2014-08-01

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

Parkinson's disease as a result of aging

PubMed Central

Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

2015-01-01

It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

PubMed

Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

2012-11-01

Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

PubMed

Fernández-Espejo, Emilio; Bis-Humbert, Cristian

2018-06-06

3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

Proton-transfer reaction mass spectrometry (PTRMS) in combination with thermal desorption (TD) for sensitive off-line analysis of volatiles.

PubMed

Crespo, Elena; Devasena, Samudrala; Sikkens, Cor; Centeno, Raymund; Cristescu, Simona M; Harren, Frans J M

2012-04-30

When performing trace gas analysis, it is not always possible to bring the source of volatiles and the gas analyzer together. In these cases, volatile storage containers, such as thermal desorption (TD) tubes, can be used for off-line measurement. TD is routinely combined with gas chromatography/mass spectrometry (GC/MS), but so far not with proton-transfer reaction mass spectrometry (PTRMS), which has a faster response. A PTR-quadrupole-MS instrument and a PTR-ion-trap-MS instrument were separately coupled to a TD unit for off-line analysis of trace volatiles in air. Carbograph 1TD/Carbopack X sorbent tubes were filled with different concentrations of a trace gas mixture containing low molecular weight volatiles (32 g/mol up to 136 g/mol) and measured with the above-mentioned combinations. The carrier gas in the TD unit was changed from helium to nitrogen to be able to combine this instrument with the mass spectrometer. Good linearity and reproducibility with the amount of gas stored were obtained. The storage capacity over time (up to 14 days) showed larger variability (<11% for all compounds, except for acetone 27%). Several tubes were filled with breath of different persons, and the breath of a smoker showed increased levels of acetonitrile and benzene. The combination of the PTR ion-trap instrument with the TD unit was also investigated. Due to its higher sampling rate, the ion-trap system showed higher throughput capabilities than the quadrupole system. The combination of TD with PTRMS using both a quadrupole and an ion trap for off-line volatile analysis has been validated. TD tubes can be a robust and compact volatile storage method when the mass spectrometry and the sampling cannot be performed in the same place, for example in large screening studies. In addition, a higher measurement throughput than with GC/MS could be obtained. Copyright © 2012 John Wiley & Sons, Ltd.

Parkinson's Disease: The Newest Advances

MedlinePlus

Skip Navigation Bar Home Current Issue Past Issues Parkinson's Disease: The Newest Advances Past Issues / Summer 2006 Table ... number of genes that cause or contribute to Parkinson's disease (PD), as well as potential environmental risk factors. ...

AV-block and conduction slowing prevail over TdP arrhythmias in the methoxamine-sensitized pro-arrhythmic rabbit model.

PubMed

Varkevisser, Rosanne; Vos, Marc A; Beekman, Jet D; Tieland, Ralph G; Van Der Heyden, Marcel A

2015-01-01

The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared currently available in-house anesthetics in order to preserve arrhythmia sensitivity and preclude conduction disturbances. Rabbits were randomly assigned to 3 groups: (1) 35 mg/kg ketamine + 5 mg/kg xylazine; (2) 0.5 mL/kg hypnorm + 3 mg/kg midazolam; (3) 35 mg/kg ketamine + 20 mg/kg propofol. Anesthesia was maintained by 1.5% isoflurane. Concomitant infusion of methoxamine (17 μg/kg/min for 40 minutes) and dofetilide (10 μg/kg/min for 30 minutes) was used to induce arrhythmias. Sole methoxamine infusion exclusively decreased HR in groups 1 and 3. Dofetilide lengthened repolarization, followed in time by PQ/QRS prolongation, second-degree AV block, and subsequently TdP arrhythmias. TdP was seen in 80%, 0%, and 33% of the rabbits in groups 1, 2, and 3, respectively. Decreasing the dose of dofetilide to 5 μg/kg/min in ketamine/xylazine anesthetized rabbits resulted in a drop in TdP incidence (25%) while conduction disturbances persisted. Flunarizine (n = 6) suppressed all TdP arrhythmias while conduction disturbances remained present. TdP incidence in the methoxamine-sensitized rabbit could be dramatically influenced by anesthesia, drug dose, and flunarizine, while conduction slowing remained present. Thus, conduction slowing seems to be the integral outcome in this model. © 2014 Wiley Periodicals, Inc.

Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

PubMed Central

Penko, Amanda L.; Hirsch, Joshua R.; Voelcker-Rehage, Claudia; Martin, Philip E.; Blackburn, Gordon; Alberts, Jay L.

2015-01-01

Background Approximately 1.5 million Americans are affected by Parkinson's disease [1] which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. Methods Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 Watt, 60 Watt, maximum performance). Findings Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 Watt and 60 Watt stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. Interpretation This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and

Moving Parkinson care to the home.

PubMed

Dorsey, E Ray; Vlaanderen, Floris P; Engelen, Lucien Jlpg; Kieburtz, Karl; Zhu, William; Biglan, Kevin M; Faber, Marjan J; Bloem, Bastiaan R

2016-09-01

In many ways, the care of individuals with Parkinson disease does not meet their needs. Despite the documented benefits of receiving care from clinicians with Parkinson disease expertise, many patients (if not most) do not. Moreover, current care models frequently require older individuals with impaired mobility, cognition, and driving ability to be driven by overburdened caregivers to large, complex urban medical centers. Moving care to the patient's home would make Parkinson disease care more patient-centered. Demographic factors, including aging populations, and social factors, such as the splintering of the extended family, will increase the need for home-based care. Technological advances, especially the ability to assess and deliver care remotely, will enable the transition of care back to the home. However, despite its promise, this next generation of home-based care will have to overcome barriers, including outdated insurance models and a technological divide. Once these barriers are addressed, home-based care will increase access to high quality care for the growing number of individuals with Parkinson disease. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Oxidation of TD nickel at 1050 C and 1200 C as compared with three grades of nickel of different purity

NASA Technical Reports Server (NTRS)

Lowell, C. E.; Grisaffe, S. J.; Deadmore, D. L.

1972-01-01

The isothermal oxidation of three nickels of different purity, Ni-200, Ni-270, and JM-Ni, was compared with that of TD-Ni in air at 1050 and 1200 C. The samples were oxidized as ground, as polished, or as annealed and polished. Weight change, metal loss, scale thickness, oxide morphology, and scale texture were determined. In degree of oxidation, TD-Ni was nearly the same as the higher purity materials, Ni-270 and JM-Ni; and less pure Ni-200 oxidized more than the others. However, in microstructure and scale texture the TD-Ni more closely resembled Ni-200. Grinding only charged the texture of the oxides of Ni_200 and TD-Ni.

Mission Management Computer and Sequencing Hardware for RLV-TD HEX-01 Mission

NASA Astrophysics Data System (ADS)

Gupta, Sukrat; Raj, Remya; Mathew, Asha Mary; Koshy, Anna Priya; Paramasivam, R.; Mookiah, T.

2017-12-01

Reusable Launch Vehicle-Technology Demonstrator Hypersonic Experiment (RLV-TD HEX-01) mission posed some unique challenges in the design and development of avionics hardware. This work presents the details of mission critical avionics hardware mainly Mission Management Computer (MMC) and sequencing hardware. The Navigation, Guidance and Control (NGC) chain for RLV-TD is dual redundant with cross-strapped Remote Terminals (RTs) interfaced through MIL-STD-1553B bus. MMC is Bus Controller on the 1553 bus, which does the function of GPS aided navigation, guidance, digital autopilot and sequencing for the RLV-TD launch vehicle in different periodicities (10, 20, 500 ms). Digital autopilot execution in MMC with a periodicity of 10 ms (in ascent phase) is introduced for the first time and successfully demonstrated in the flight. MMC is built around Intel i960 processor and has inbuilt fault tolerance features like ECC for memories. Fault Detection and Isolation schemes are implemented to isolate the failed MMC. The sequencing hardware comprises Stage Processing System (SPS) and Command Execution Module (CEM). SPS is `RT' on the 1553 bus which receives the sequencing and control related commands from MMCs and posts to downstream modules after proper error handling for final execution. SPS is designed as a high reliability system by incorporating various fault tolerance and fault detection features. CEM is a relay based module for sequence command execution.

Sleep disorders and Parkinson disease; lessons from genetics.

PubMed

Gan-Or, Ziv; Alcalay, Roy N; Rouleau, Guy A; Postuma, Ronald B

2018-01-31

Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Correlated regions of cerebral blood flow with clinical parameters in Parkinson's disease; comparison using 'Anatomy' and 'Talairach Daemon' software.

PubMed

Yoon, Hyun Jin; Cheon, Sang Myung; Jeong, Young Jin; Kang, Do-Young

2012-02-01

We assign the anatomical names of functional activation regions in the brain, based on the probabilistic cyto-architectonic atlas by Anatomy 1.7 from an analysis of correlations between regional cerebral blood flow (rCBF) and clinical parameters of the non-demented Parkinson's disease (PD) patients by SPM8. We evaluated Anatomy 1.7 of SPM toolbox compared to 'Talairach Daemon' (TD) Client 2.4.2 software. One hundred and thirty-six patients (mean age 60.0 ± 9.09 years; 73 women and 63 men) with non-demented PD were selected. Tc-99m-HMPAO brain single-photon emission computed tomography (SPECT) scans were performed on the patients using a two-head gamma-camera. We analyzed the brain image of PD patients by SPM8 and found the anatomical names of correlated regions of rCBF perfusion with the clinical parameters using TD Client 2.4.2 and Anatomy 1.7. The SPM8 provided a correlation coefficient between clinical parameters and cerebral hypoperfusion by a simple regression method. To the clinical parameters were added age, duration of disease, education period, Hoehn and Yahr (H&Y) stage and Korean mini-mental state examination (K-MMSE) score. Age was correlated with cerebral perfusion in the Brodmann area (BA) 6 and BA 3b assigned by Anatomy 1.7 and BA 6 and pyramis in gray matter by TD Client 2.4.2 with p < 0.001 uncorrected. Also, assigned significant correlated regions were found in the left and right lobules VI (Hem) with duration of disease, in left and right lobules VIIa crus I (Hem) with education, in left insula (Ig2), left and right lobules VI (Hem) with H&Y, and in BA 4a and 6 with K-MMSE score with p < 0.05 uncorrected by Anatomy 1.7, respectively. Most areas of correlation were overlapped by two different anatomical labeling methods, but some correlation areas were found with different names. Age was the most significantly correlated clinical parameter with rCBF. TD Client found the exact anatomical name by the peak intensity position of the cluster while

Proposed Project Selection Method for Human Support Research and Technology Development (HSR&TD)

NASA Technical Reports Server (NTRS)

Jones, Harry

2005-01-01

The purpose of HSR&TD is to deliver human support technologies to the Exploration Systems Mission Directorate (ESMD) that will be selected for future missions. This requires identifying promising candidate technologies and advancing them in technology readiness until they are acceptable. HSR&TD must select an may of technology development projects, guide them, and either terminate or continue them, so as to maximize the resulting number of usable advanced human support technologies. This paper proposes an effective project scoring methodology to support managing the HSR&TD project portfolio. Researchers strongly disagree as to what are the best technology project selection methods, or even if there are any proven ones. Technology development is risky and outstanding achievements are rare and unpredictable. There is no simple formula for success. Organizations that are satisfied with their project selection approach typically use a mix of financial, strategic, and scoring methods in an open, established, explicit, formal process. This approach helps to build consensus and develop management insight. It encourages better project proposals by clarifying the desired project attributes. We propose a project scoring technique based on a method previously used in a federal laboratory and supported by recent research. Projects are ranked by their perceived relevance, risk, and return - a new 3 R's. Relevance is the degree to which the project objective supports the HSR&TD goal of developing usable advanced human support technologies. Risk is the estimated probability that the project will achieve its specific objective. Return is the reduction in mission life cycle cost obtained if the project is successful. If the project objective technology performs a new function with no current cost, its return is the estimated cash value of performing the new function. The proposed project selection scoring method includes definitions of the criteria, a project evaluation

Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson's Disease.

PubMed

Gao, Chao; Sun, Hanbo; Wang, Tuo; Tang, Ming; Bohnen, Nicolaas I; Müller, Martijn L T M; Herman, Talia; Giladi, Nir; Kalinin, Alexandr; Spino, Cathie; Dauer, William; Hausdorff, Jeffrey M; Dinov, Ivo D

2018-05-08

In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.

Adaptation of the TdT assay for semi-quantitative flow cytometric detection of DNA strand breaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bromidge, T.J.; Howe, D.J.; Johnson, S.A.

The enzyme Terminal Deoxynucleotidyl Transferase (TdT) is a DNA polymerase which can be used to label DNA strand breaks by the incorporation of a labelled nucleotide followed by a fluorescent detection step. The amount of label incorporated can then be assessed by flow cytometry. The mechanism of action of TdT, however, will allow the addition of varying numbers of nucleotides to the free 3{prime} termini produced by DNA strand breaks. The substitution of Digoxigenin (DIG){trademark} labelled dideoxynucleotides for labelled deoxy-nucleotides in the TdT assay will limit the addition of label to a DNA break to a single nucleotide, thus ensuringmore » a direct relationship between an increase in DNA strand breaks and an increase in fluorescence. We have used this adaptation of the TdT assay to evaluate DNA damage incurred in lymphocytes, from patients with Chronic Lymphocytic Leukemia (CLL), on exposure to UV irradiation and apoptosis-inducing drugs, fludarabine and 2-Chloro-2{prime}-deoxyadenosine (2-CdA). This technique may give a good indication of the susceptibility of CLL patients to apoptosis inducing drugs, and hence an indication of the likely response to these therapies. 7 refs., 2 figs., 2 tabs.« less

Using SpaceClaim/TD Direct for Modeling Components with Complex Geometries for the Thermal Desktop-Based Advanced Stirling Radioisotope Generator Model

NASA Technical Reports Server (NTRS)

Fabanich, William

2014-01-01

SpaceClaim/TD Direct has been used extensively in the development of the Advanced Stirling Radioisotope Generator (ASRG) thermal model. This paper outlines the workflow for that aspect of the task and includes proposed best practices and lessons learned. The ASRG thermal model was developed to predict component temperatures and power output and to provide insight into the prime contractors thermal modeling efforts. The insulation blocks, heat collectors, and cold side adapter flanges (CSAFs) were modeled with this approach. The model was constructed using mostly TD finite difference (FD) surfaces solids. However, some complex geometry could not be reproduced with TD primitives while maintaining the desired degree of geometric fidelity. Using SpaceClaim permitted the import of original CAD files and enabled the defeaturing repair of those geometries. TD Direct (a SpaceClaim add-on from CRTech) adds features that allowed the mark-up of that geometry. These so-called mark-ups control how finite element (FE) meshes were generated and allowed the tagging of features (e.g. edges, solids, surfaces). These tags represent parameters that include: submodels, material properties, material orienters, optical properties, and radiation analysis groups. TD aliases were used for most tags to allow analysis to be performed with a variety of parameter values. Domain-tags were also attached to individual and groups of surfaces and solids to allow them to be used later within TD to populate objects like, for example, heaters and contactors. These tools allow the user to make changes to the geometry in SpaceClaim and then easily synchronize the mesh in TD without having to redefine these objects each time as one would if using TD Mesher.The use of SpaceClaim/TD Direct has helped simplify the process for importing existing geometries and in the creation of high fidelity FE meshes to represent complex parts. It has also saved time and effort in the subsequent analysis.

Is the Parkinson Anxiety Scale comparable across raters?

PubMed

Forjaz, Maria João; Ayala, Alba; Martinez-Martin, Pablo; Dujardin, Kathy; Pontone, Gregory M; Starkstein, Sergio E; Weintraub, Daniel; Leentjens, Albert F G

2015-04-01

The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test-retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C. © 2014 International Parkinson and Movement Disorder Society.

Vaccination strategies for Parkinson disease

PubMed Central

Romero-Ramos, Marina; von Euler Chelpin, Marianne; Sanchez-Guajardo, Vanesa

2014-01-01

Parkinson disease is the second most common neurodegenerative disease in the world, but there is currently no available cure for it. Current treatments only alleviate some of the symptoms for a few years, but they become ineffective in the long run and do not stop the disease. Therefore it is of outmost importance to develop therapeutic strategies that can prevent, stop, or cure Parkinson disease. A very promising target for these therapies is the peripheral immune system due to its probable involvement in the disease and its potential as a tool to modulate neuroinflammation. But for such strategies to be successful, we need to understand the particular state of the peripheral immune system during Parkinson disease in order to avoid its weaknesses. In this review we examine the available data regarding how dopamine regulates the peripheral immune system and how this regulation is affected in Parkinson disease; the specific cytokine profiles observed during disease progression and the alterations documented to date in patients’ peripheral blood mononuclear cells. We also review the different strategies used in Parkinson disease animal models to modulate the adaptive immune response to salvage dopaminergic neurons from cell death. After analyzing the evidence, we hypothesize the need to prime the immune system to restore natural tolerance against α-synuclein in Parkinson disease, including at the same time B and T cells, so that T cells can reprogram microglia activation to a beneficial pattern and B cell/IgG can help neurons cope with the pathological forms of α-synuclein. PMID:24670306

Users manual and modeling improvements for axial turbine design and performance computer code TD2-2

NASA Technical Reports Server (NTRS)

Glassman, Arthur J.

1992-01-01

Computer code TD2 computes design point velocity diagrams and performance for multistage, multishaft, cooled or uncooled, axial flow turbines. This streamline analysis code was recently modified to upgrade modeling related to turbine cooling and to the internal loss correlation. These modifications are presented in this report along with descriptions of the code's expanded input and output. This report serves as the users manual for the upgraded code, which is named TD2-2.

Pragmatic communication is impaired in Parkinson disease.

PubMed

Hall, Deborah; Ouyang, Bichun; Lonnquist, Eryn; Newcombe, Jill

2011-05-01

The purpose of this study was to determine whether severity of disease, cognitive function, age, gender, or amount of social interaction were associated with pragmatic dysfunction in Parkinson disease. No studies have previously been done to investigate variables that may be associated with pragmatic dysfunction in Parkinson disease. A case-control study was conducted with 17 Parkinson disease patients and 17 convenience controls. Each Parkinson disease patient and a control were interviewed, and their pragmatic skills were evaluated using a scale of pragmatic communication skills. Correlation analysis was used to determine what factors were associated with pragmatic dysfunction in the Parkinson disease patients. Cases scored lower on the pragmatic scale with a mean of 29.7 compared with 38.9 in the controls (p < .001) out of 40 possible points. The score on the scale of pragmatic communication skills had moderate to strong correlations with the MMSE (r = .81, p = .002), Unified Parkinson's Disease Rating Scale score (r = -.71, p = .002), and duration of disease (r = -.53, p = .03). These results show that Parkinson disease patients have impaired pragmatic function compared with controls on both verbal and nonverbal sections, and this impairment correlates with mental state, duration, and severity of disease.

Stimulus Timing by People with Parkinson's Disease

ERIC Educational Resources Information Center

Wearden, J. H.; Smith-Spark, J. H.; Cousins, Rosanna; Edelstyn, N. M. J.; Cody, F. W. J.; O'Boyle, D. J.

2008-01-01

Previous literature suggests that Parkinson's disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson's disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson's…

The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study.

PubMed

Zhang, Li; Li, Tian-Nv; Yuan, Yong-Sheng; Jiang, Si-Ming; Tong, Qing; Wang, Min; Wang, Jian-Wei; Chen, Hua-Jun; Ding, Jian; Xu, Qin-Rong; Zhang, Ke-Zhong

2016-05-01

The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease. With F-18 fluorodeoxyglucose PET (FDG-PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor-dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom-correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI. Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed-based FC analysis. Decreased FC within the prefrontal-parietal network (between the MFG and IPL) was associated with severe PIGD symptoms. The involvement of the caudate, FG, and prefrontal-parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders. © 2016 John Wiley & Sons Ltd.

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

High rates of parkinsonism in adults with autism.

PubMed

Starkstein, Sergio; Gellar, Scott; Parlier, Morgan; Payne, Leslie; Piven, Joseph

2015-01-01

While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson's disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson's disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism.

Increased risk of parkinsonism associated with welding exposure

PubMed Central

Racette, Brad A.; Criswell, Susan R.; Lundin, Jessica I.; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T.; Evanoff, Bradley A.; Perlmutter, Joel S.; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2013-01-01

Objective Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. Methods This was a cross-sectional and nested case–control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3 < 6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. Results The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose–response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. Conclusion This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. PMID:22975422

[The experimental models of Parkinson's disease in animals].

PubMed

Grigor'ian, G A; Bazian, A S

2007-01-01

The current review describes the modem Parkinson's disease models in animals, their advantages, limitations and disadvantages. It was noted that the most widespread up-to-date models based on etiology of the Parkinson's disease. Although toxins mostly produce the Parkinson's disease, a study of involved genes allows investigating not only inherited but also sporadic (not inherited) forms of disease since the same genes are involved in both cases. Mutations of genes lead to formation of "mutant" toxic proteins, which produce a death of the specialized neurons of the nigrostriatal dopaminergic system and the development of Parkinson's disease. A significant place in the review takes adescription of characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their similarities and differences in pathogenetic mechanisms of the Parkinson's disease development. On the basis of the considered experimental models of Parkinson's disease a conclusion has been done that none of these models may in full and adequate scale imitate the entire clinical, pathophysiological, morphological, biochemical and other aspects of the Parkinson's disease development.

Development of a HTS transceiver sub-system for 3G mobile communication TD-SCDMA base station

NASA Astrophysics Data System (ADS)

Zhang, Xueqiang; He, Xiaofeng; Wang, Yuehui; Duan, Tao; Wang, Guizhen; Zhang, Yan; Li, Chunguang; Zhang, Qiang; Li, Hong; He, Yusheng

2010-02-01

A prototype of a high temperature superconducting (HTS) transceiver sub-system for applications in a TD-SCDMA, one of the third generation (3G) communication standards, base station has been developed. Both the HTS sub-system and the conventional counterpart have been implemented into a TD-SCDMA commercial communication network and comparison test studies were carried out. The measured results showed that the HTS sub-system could remarkably improve the RF performance of both transmitting and receiving chains.

Great shakes: famous people with Parkinson disease.

PubMed

Jones, Jeffrey M

2004-12-01

James Parkinson is credited with the first complete clinical description of the syndrome attributed to his name, Parkinson disease. It is recognized as the first syndrome defined after neurology became a specialty. Descriptions of Parkinson features are rare in antiquity, and famous people with this disorder have not been found before the 1800s. During the 20th century, more and more famous people appear to be afflicted with Parkinson, and this article reviews some of those who have withstood the "test of Time magazine," and examines some of the reasons why the syndrome is a relatively recent disorder.

Virtual house calls for Parkinson disease (Connect.Parkinson): study protocol for a randomized, controlled trial.

PubMed

Achey, Meredith A; Beck, Christopher A; Beran, Denise B; Boyd, Cynthia M; Schmidt, Peter N; Willis, Allison W; Riggare, Sara S; Simone, Richard B; Biglan, Kevin M; Dorsey, E Ray

2014-11-27

Interest in improving care for the growing number of individuals with chronic conditions is rising. However, access to care is limited by distance, disability, and distribution of doctors. Small-scale studies in Parkinson disease, a prototypical chronic condition, have suggested that delivering care using video house calls is feasible, offers similar clinical outcomes to in-person care, and reduces travel burden. We are conducting a randomized comparative effectiveness study (Connect.Parkinson) comparing usual care in the community to usual care augmented by virtual house calls with a Parkinson disease specialist. Recruitment is completed centrally using online advertisements and emails and by contacting physicians, support groups, and allied health professionals. Efforts target areas with a high proportion of individuals not receiving care from neurologists. Approximately 200 individuals with Parkinson disease and their care partners will be enrolled at 20 centers throughout the United States and followed for one year. Participants receive educational materials, then are randomized in a 1:1 ratio to continue their usual care (control arm) or usual care and specialty care delivered virtually (intervention arm). Care partners are surveyed about their time and travel burden and their perceived caregiver burden. Participants are evaluated via electronic survey forms and videoconferencing with a blinded independent rater at baseline and at 12 months. All study activities are completed remotely.The primary outcomes are: (1) feasibility, as measured by the proportion of visits completed, and (2) quality of life, as measured by the 39-item Parkinson's Disease Questionnaire. Secondary outcomes include measures of clinical benefit, quality of care, time and travel burden, and caregiver burden. Connect.Parkinson will evaluate the feasibility and effectiveness of using technology to deliver care into the homes of individuals with Parkinson disease. The trial may serve as a

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Longitudinal Study of Gray Matter Changes in Parkinson Disease.

PubMed

Jia, X; Liang, P; Li, Y; Shi, L; Wang, D; Li, K

2015-12-01

The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis. Longitudinal cognitive assessment and structural MR imaging of 89 patients with Parkinson disease (62 men) and 55 healthy controls (33 men) were from the Parkinson's Progression Markers Initiative data base, including the initial baseline and 12-month follow-up data. Two-way analysis of covariance was performed with covariates of age, sex, years of education, imaging data from multiple centers, and total intracranial volume by using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra tool from SPM8 software. Gray matter volume changes for patients with Parkinson disease were detected with decreased gray matter volume in the frontotemporoparietal areas and the bilateral caudate, with increased gray matter volume in the bilateral limbic/paralimbic areas, medial globus pallidus/putamen, and the right occipital cortex compared with healthy controls. Progressive gray matter volume decrease in the bilateral caudate was found for both patients with Parkinson disease and healthy controls, and this caudate volume was positively associated with cognitive ability for both groups. The progressive gray matter volume increase specific to the patients with Parkinson disease was identified close to the left ventral lateral nucleus of thalamus, and a positive relationship was found between the thalamic volume and the tremor scores in a subgroup with tremor-dominant patients with Parkinson disease. The observed progressive changes in gray matter volume in Parkinson disease may provide

Managing Parkinson's

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Foundation

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Increased risk of parkinsonism associated with welding exposure.

PubMed

Racette, Brad A; Criswell, Susan R; Lundin, Jessica I; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T; Evanoff, Bradley A; Perlmutter, Joel S; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2012-10-01

Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. This was a cross-sectional and nested case-control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3<6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose-response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. Copyright © 2012 Elsevier Inc. All rights reserved.

A case of Parkinson's disease following dystonia.

PubMed

Yasuda, Chiharu; Takei, Takanobu; Uozumi, Takenori; Toyota, Tomoko; Yuhi, Tomoaki; Adachi, Hiroaki

2016-09-29

Parkinsonism and dystonia are both disorders of the extrapyramidal motor system, and some patients exhibit a complex of the two symptoms. Although several reports have referred to the coexistence of these disorders as parkinsonian disorders with dystonia, in the majority of cases, dystonia appeared after parkinsonism. DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other types of parkinsonism such as dementia with Lewy bodies. This case report describes a 67-year old woman diagnosed with axial dystonia without parkinsonism 6 years previously, which had worsened despite treatment with Botulinum toxin injections, and hindered the patient's gait. The patient visited the hospital because of gait disturbances and DAT-scan showed a levodopa transducer decrease in the putamen. A few weeks later, she was re-admitted to hospital and exhibited Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this was a rare case of parkinsonian disorders with dystonia, characterized by the development of PD after dystonia. DAT-scan may be helpful for the diagnosis of patients with parkinsonian disorders with dystonia.

Dream Robber: Living with Parkinson's disease

MedlinePlus

... Current Issue Past Issues Dream Robber: Living with Parkinson's disease Past Issues / Summer 2006 Table of Contents For ... Now 65, he has been permanently grounded by Parkinson's disease, unable, due to the loss of motor control ...

Caribbean parkinsonism and other atypical parkinsonian disorders.

PubMed

Tolosa, Eduardo; Calandrella, Daniela; Gallardo, Marisol

2004-05-01

Atypical parkinsonism (AP) is a term applied to disorders characterized by parkinsonism that evolves rapidly, with poor or transient response to levodopa, or has other associated features such as early falls and postural instability, early autonomic failure, supranuclear gaze palsy, pyramidal or cerebellar signs, alien hand syndrome or severe ideomotor apraxia. The most common AP are multiple system atrophy, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Other APs include Caribbean parkinsonism (CP) and parkinsonism-dementia complex of Guam (PDC). In this review we provide an update in etiology, neuropathology, diagnosis and treatment of atypical parkinsonian disorders associated with protein tau deposit, also known as tauopathies.

Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poduslo, S.E.; Schwankhaus, J.D.

1994-09-01

A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal,more » and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.« less

Signal-on electrochemical assay for label-free detection of TdT and BamHI activity based on grown DNA nanowire-templated copper nanoclusters.

PubMed

Hu, Yufang; Zhang, Qingqing; Xu, Lihua; Wang, Jiao; Rao, Jiajia; Guo, Zhiyong; Wang, Sui

2017-11-01

Electrochemical methods allow fast and inexpensive analysis of enzymatic activity. Here, a simple and yet efficient "signal-on" electrochemical assay for sensitive, label-free detection of DNA-related enzyme activity was established on the basis of terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. TdT, which is a template-independent DNA polymerase, can catalyze the sequential addition of deoxythymidine triphosphate (dTTP) at the 3'-OH terminus of single-stranded DNA (ssDNA); then, the TdT-yield T-rich DNA nanowires can be employed as the synthetic template of copper nanoclusters (CuNCs). Grown DNA nanowires-templated CuNCs (noted as DNA-CuNCs) were attached onto graphene oxide (GO) surface and exhibited unique electrocatalytic activity to H 2 O 2 reduction. Under optimal conditions, the proposed biosensor was utilized for quantitatively monitoring TdT activity, with the observed LOD of 0.1 U/mL. It also displayed high selectivity to TdT with excellent stability, and offered a facile, convenient electrochemical method for TdT-relevant inhibitors screening. Moreover, the proposed sensor was successfully used for BamHI activity detection, in which a new 3'-OH terminal was exposed by the digestion of a phosphate group. Ultimately, it has good prospects in DNA-related enzyme-based biochemical studies, disease diagnosis, and drug discovery. Graphical Abstract Extraordinary TdT-generated DNA-CuNCs are synthesized and act as a novel electrochemical sensing platform for sensitive detection of TdT and BamHI activity in biological environments.

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

PubMed

Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2008-04-18

Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Using SpaceClaimTD Direct for Modeling Components with Complex Geometries for the Thermal Desktop-Based Advanced Stirling Radioisotope Generator Model

NASA Technical Reports Server (NTRS)

Fabanich, William A., Jr.

2014-01-01

SpaceClaim/TD Direct has been used extensively in the development of the Advanced Stirling Radioisotope Generator (ASRG) thermal model. This paper outlines the workflow for that aspect of the task and includes proposed best practices and lessons learned. The ASRG thermal model was developed to predict component temperatures and power output and to provide insight into the prime contractor's thermal modeling efforts. The insulation blocks, heat collectors, and cold side adapter flanges (CSAFs) were modeled with this approach. The model was constructed using mostly TD finite difference (FD) surfaces/solids. However, some complex geometry could not be reproduced with TD primitives while maintaining the desired degree of geometric fidelity. Using SpaceClaim permitted the import of original CAD files and enabled the defeaturing/repair of those geometries. TD Direct (a SpaceClaim add-on from CRTech) adds features that allowed the "mark-up" of that geometry. These so-called "mark-ups" control how finite element (FE) meshes are to be generated through the "tagging" of features (e.g. edges, solids, surfaces). These tags represent parameters that include: submodels, material properties, material orienters, optical properties, and radiation analysis groups. TD aliases were used for most tags to allow analysis to be performed with a variety of parameter values. "Domain-tags" were also attached to individual and groups of surfaces and solids to allow them to be used later within TD to populate objects like, for example, heaters and contactors. These tools allow the user to make changes to the geometry in SpaceClaim and then easily synchronize the mesh in TD without having to redefine the objects each time as one would if using TDMesher. The use of SpaceClaim/TD Direct helps simplify the process for importing existing geometries and in the creation of high fidelity FE meshes to represent complex parts. It also saves time and effort in the subsequent analysis.

Recent developments in biomarkers in Parkinson disease

PubMed Central

Schapira, Anthony H.V.

2013-01-01

Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

In Vitro Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species

PubMed Central

Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.

2012-01-01

TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of Corynebacterium species. Against nearly all Gram-positive strains, TD-1792 had an MIC90 of 0.25 μg/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin. PMID:22290981

RNA chaperone StpA loosens interactions of the tertiary structure in the td group I intron in vivo

PubMed Central

Waldsich, Christina; Grossberger, Rupert; Schroeder, Renée

2002-01-01

Efficient splicing of the td group I intron in vivo is dependent on the ribosome. In the absence of translation, the pre-mRNA is trapped in nonnative-splicing-incompetent conformations. Alternatively, folding of the pre-mRNA can be promoted by the RNA chaperone StpA or by the group I intron-specific splicing factor Cyt-18. To understand the mechanism of action of RNA chaperones, we probed the impact of StpA on the structure of the td intron in vivo. Our data suggest that StpA loosens tertiary interactions. The most prominent structural change was the opening of the base triples, which are involved in the correct orientation of the two major intron core domains. In line with the destabilizing activity of StpA, splicing of mutant introns with a reduced structural stability is sensitive to StpA. In contrast, Cyt-18 strengthens tertiary contacts, thereby rescuing splicing of structurally compromised td mutants in vivo. Our data provide direct evidence for protein-induced conformational changes within catalytic RNA in vivo. Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18 contributes to the overall compactness of the td intron in vivo. PMID:12208852

Mobility spectrum analytical approach for the type-II Weyl semimetal Td-MoTe2

NASA Astrophysics Data System (ADS)

Pei, Q. L.; Luo, X.; Chen, F. C.; Lv, H. Y.; Sun, Y.; Lu, W. J.; Tong, P.; Sheng, Z. G.; Han, Y. Y.; Song, W. H.; Zhu, X. B.; Sun, Y. P.

2018-02-01

The extreme magnetoresistance (XMR) in orthorhombic W/MoTe2 arises from the combination of the perfect electron-hole (e-h) compensation effect and the unique orbital texture topology, which have comprised an intriguing research field in materials physics. Herein, we apply a special analytical approach as a function of mobility (μ-spectrum) without any hypothesis. Based on the interpretations of longitudinal and transverse electric transport of Td-MoTe2, the types and the numbers of carriers can be obtained. There are three observations: the large residual resistivity ratio can be observed in the MoTe2 single crystal sample, which indicates that the studied crystal is of high quality; we observed three electron-pockets and three hole-ones from the μ-spectrum and that the ratio of h/e is much less than 1, which shows that MoTe2 is more e-like; different from the separated peaks obtained from the hole-like μ-spectrum, those of the electron-like one are continuous, which may indicate the topological feature of electron-pockets in Td-MoTe2. The present results may provide an important clue to understanding the mechanism of the XMR effect in Td-MoTe2.

Pharmacotherapy for Parkinson's disease.

PubMed

Chen, Jack J; Swope, David M

2007-12-01

The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short-term benefits as well as long-term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well-tolerated agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence of functional impairment is associated with improved long-term outcomes. Consideration should also be given to many patient-specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered. For management of levodopa-induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.

Placebo influences on dyskinesia in Parkinson's disease.

PubMed

Goetz, Christopher G; Laska, Eugene; Hicking, Christine; Damier, Philippe; Müller, Thomas; Nutt, John; Warren Olanow, C; Rascol, Olivier; Russ, Hermann

2008-04-15

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, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. 2007 Movement Disorder Society

Placebo Influences on Dyskinesia in Parkinson's Disease

PubMed Central

Goetz, Christopher G.; Laska, Eugene; Hicking, Christine; Damier, Philippe; Müller, Thomas; Nutt, John; Olanow, C. Warren; Rascol, Olivier; Russ, Hermann

2009-01-01

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, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. PMID:18175337

Oxidation behavior of TD-NiCr in a dynamic high temperature environment

NASA Technical Reports Server (NTRS)

Tenney, D. R.; Young, C. T.; Herring, H. W.

1974-01-01

The oxidation behavior of TD-NiCr has been studied in static and high-speed flowing air environments at 1100 and 1200 C. It has been found that the stable oxide morphologies formed on the specimens exposed to the static and dynamic environments were markedly different. The faceted crystal morphology characteristic of static oxidation was found to be unstable under high-temperature, high-speed flow conditions and was quickly replaced by a porous NiO 'mushroom' type structure. Also, it was found that the rate of formation of CrO3 from Cr2O3 was greatly enhanced by high gas velocity conditions. The stability of Cr2-O3 was found to be greatly improved by the presence of an outer NiO layer, even though the NiO layer was very porous. An oxidation model is proposed to explain the observed microstructures and overall oxidation behavior of TD-NiCr alloys.

Absence of Change in Total Daily Energy Expenditure (EE(sub TD)) in Young and Mature Rats During 14 Days of Hypergravity

NASA Technical Reports Server (NTRS)

Wade, C. E.; Moran, M. M.; Stein, T. P.; Hoban-Higgins, T. M.; Fuller, P.; Fuller, C. A.; Dalton, Bonnie P. (Technical Monitor)

1999-01-01

Effect of age on the response of EE(sub TD) to an increase in gravity was assessed in young (Y; 1.5 month old) and mature (M; 8 month old) Sprague-Dawley rats. Rats were implanted with transmitters to monitor activity, and metabolism was determined by the double labeled water technique. Daily food intake was measured. For each age, rats (n=8 per treatment) were exposed to centrifugation at 2G, or remained at 1G. There was a difference in EE(sub TD) between age groups, 182 plus or minus 11 and 143 plus or minus 5 kcal/kg/day in Y and M, respectively. This difference was attributed in part to a lower activity level in M animals, 48% of Y rats. After day 6 there was no effect on EE(sub TD) of exposure to 2G, or on food intake per 100g BW. Prior studies show a 20% increase in resting EE with hypergravity. In our study the level of activity was reduced to 41% of 1G in both age groups during 2G. For Y at 1G resting EE accounted for 78% of the EE(sub TD) and activity 22%, while at 2G resting EE was 96% of EE(sub TD) and activity 4%. M rats had similar changes. Independent of age, with exposure to hypergravity EE(sub TD) is maintained by behavioral changes.

The frequency of buccopalpebral reflex in Parkinson disease.

PubMed

Eser, Hülya; Ünal, Yasemin; Kutlu, Gülnihal; Öcal, Ruhsen; İnan, Levent Ertuğrul

2016-11-17

This study aimed to define the frequency of a primitive reflex, the buccopalpebral reflex (BPR), and its association with the clinical situation in patients with Parkinson disease. Between May 2010 and May 2011, 222 patients, 115 with Parkinson disease and 107 patients without any sign of neurodegenerative disease, were included in the study. All included patients were examined for BPR and snout reflex and were also evaluated with the Mini Mental State Examination. All patients with Parkinson disease were classified with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Score to determine their clinical severity. Sixteen patients with Parkinson disease (13.9%) had a BPR (+) and 4 patients in the control group (3.7%) (P < 0.001). The UPDRS score, UPDRS daily life activities score, and UPDRS motor system score were all higher in the group with BPR (+). All patients with a BPR also had a positive snout reflex. BPR is more frequent in patients with Parkinson disease than in patients without a neurodegenerative disease.

Protein Kinases and Parkinson's Disease.

PubMed

Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Barger, Steven W; Sarkar, Sumit; Paule, Merle G; Ali, Syed F; Imam, Syed Z

2016-09-20

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson's disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson's disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson's disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.

Neuromuscular rate of force development deficit in Parkinson disease.

PubMed

Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

[Prevention and Treatment of Common Acute Adverse Effects With Antipsychotic Use in Adults With Schizophrenia Diagnosis].

PubMed

Arenas Borrero, Álvaro Enrique; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Vélez Traslaviña, Ángela; Castro Díaz, Sergio Mario; Jaramillo González, Luis Eduardo; García Valencia, Jenny

2014-01-01

To determine the most adequate strategies for the prevention and treatment of the acute adverse effects of the use of antipsychotics. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. A systematic literature search was carried out. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The non-pharmacological interventions such as nutritional counseling by a nutritionist, exercise and psychotherapy are effective in preventing weight gain with the use of antipsychotics. (Kg Weight reduction in DM of -3.05 (-4.16, -1.94)). The antipsychotic change from olanzapine to aripiprazole showed weight loss and decreased BMI (decreased weight in KG DM -3.21 (-9.03, -2.61). The use of beta blockers was ineffective in reducing akathisia induced by antipsychotic; using as outcome the 50% reduction of symptoms of akathisia comparing beta-blockers with placebo RR was 1.4 (0.59, 1.83). It is recommended to make psychotherapeutic accompaniment and nutrition management of overweight for patients with weight gain. If these alternatives are ineffective is suggested to change the antipsychotic or consider starting metformin. For the management of drug-induced akathisia it is recommended to decrease the dose of the drug and the addition of lorazepam. It is recommended using 5mg biperiden IM or trihexyphenidyl 5mg orally in case of secondary acute dystonia and for the treatment of antipsychotic-induced parkinsonism to decrease the dose of antipsychotic or consider using 2 - 4mg/day of biperiden or diphenhydramine 50mg once daily. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Vocal tract characteristics in Parkinson's disease.

PubMed

Gillivan-Murphy, Patricia; Carding, Paul; Miller, Nick

2016-06-01

Voice tremor is strongly linked to the Parkinson's disease speech-voice symptom complex. Little is known about the underlying anatomic source(s) of voice tremor when it occurs. We review recent literature addressing this issue. Additionally we report findings from a study we conducted employing rating of vocal tract structures viewed using nasolaryngoscopy during vocal and nonspeech tasks. In Parkinson's disease, using laryngeal electromyography, tremor has not been identified in muscles in the vocal folds even when perceived auditorily. Preliminary findings using nasolaryngoscopy suggest that Parkinson's disease voice tremor is not associated with the vocal folds and may involve the palate, the global larynx, and the arytenoids. Tremor in the vertical larynx on /a/, and tremor in the arytenoid cartilages on /s/ differentiated patients with Parkinson's disease from neurologically healthy controls. Visual reliable detection of tremor when it is absent or borderline present, is challenging. Parkinson's disease voice tremor is likely to be related to oscillatory movement in structures across the vocal tract rather than just the vocal folds. To progress clinical practice, more refined tools for the visual rating of tremor would be beneficial. How far voice tremor represents a functionally significant factor for speakers would also add to the literature.

Positive Selection and Multiple Losses of the LINE-1-Derived L1TD1 Gene in Mammals Suggest a Dual Role in Genome Defense and Pluripotency

PubMed Central

Yang, Lei; Neme, Rafik; Wichman, Holly A.; Malik, Harmit S.

2014-01-01

Mammalian genomes comprise many active and fossilized retroelements. The obligate requirement for retroelement integration affords host genomes an opportunity to ‘domesticate’ retroelement genes for their own purpose, leading to important innovations in genome defense and placentation. While many such exaptations involve retroviruses, the L1TD1 gene is the only known domesticated gene whose protein-coding sequence is almost entirely derived from a LINE-1 (L1) retroelement. Human L1TD1 has been shown to play an important role in pluripotency maintenance. To investigate how this role was acquired, we traced the origin and evolution of L1TD1. We find that L1TD1 originated in the common ancestor of eutherian mammals, but was lost or pseudogenized multiple times during mammalian evolution. We also find that L1TD1 has evolved under positive selection during primate and mouse evolution, and that one prosimian L1TD1 has ‘replenished’ itself with a more recent L1 ORF1 from the prosimian genome. These data suggest that L1TD1 has been recurrently selected for functional novelty, perhaps for a role in genome defense. L1TD1 loss is associated with L1 extinction in several megabat lineages, but not in sigmodontine rodents. We hypothesize that L1TD1 could have originally evolved for genome defense against L1 elements. Later, L1TD1 may have become incorporated into pluripotency maintenance in some lineages. Our study highlights the role of retroelement gene domestication in fundamental aspects of mammalian biology, and that such domesticated genes can adopt different functions in different lineages. PMID:25211013

Parkinson's disease - the story of an eponym.

PubMed

Goedert, Michel; Compston, Alastair

2018-01-01

One of the most prevalent neurodegenerative diseases worldwide is still referred to as 'Parkinson's disease'. The condition is named after James Parkinson who, in 1817, described the shaking palsy (paralysis agitans). In the bicentennial year of this publication, we trace when and why the shaking palsy became Parkinson's disease. The term was coined by William Rutherford Sanders of Edinburgh in 1865 and later entered general usage through the influence of Jean-Martin Charcot and the school that he nurtured at the Salpêtrière Hospital in Paris. Despite a move towards more mechanism-based nosology for many medical conditions in recent years, the Parkinson's disease eponym remains in place, celebrating the life and work of this doctor, palaeontologist and political activist.

Spectral densities for Frenkel exciton dynamics in molecular crystals: A TD-DFTB approach

NASA Astrophysics Data System (ADS)

Plötz, Per-Arno; Megow, Jörg; Niehaus, Thomas; Kühn, Oliver

2017-02-01

Effects of thermal fluctuations on the electronic excitation energies and intermonomeric Coulomb couplings are investigated for a perylene-tetracarboxylic-diimide crystal. To this end, time dependent density functional theory based tight binding (TD-DFTB) in the linear response formulation is used in combination with electronic ground state classical molecular dynamics. As a result, a parametrized Frenkel exciton Hamiltonian is obtained, with the effect of exciton-vibrational coupling being described by spectral densities. Employing dynamically defined normal modes, these spectral densities are analyzed in great detail, thus providing insight into the effect of specific intramolecular motions on excitation energies and Coulomb couplings. This distinguishes the present method from approaches using fixed transition densities. The efficiency by which intramolecular contributions to the spectral density can be calculated is a clear advantage of this method as compared with standard TD-DFT.

Parkinson's Disease

MedlinePlus

Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

Diagnostic Value of the Impairment of Olfaction in Parkinson's Disease

PubMed Central

Casjens, Swaantje; Eckert, Angelika; Woitalla, Dirk; Ellrichmann, Gisa; Turewicz, Michael; Stephan, Christian; Eisenacher, Martin; May, Caroline; Meyer, Helmut E.; Brüning, Thomas; Pesch, Beate

2013-01-01

Background Olfactory impairment is increasingly recognized as an early symptom in the development of Parkinson's disease. Testing olfactory function is a non-invasive method but can be time-consuming which restricts its application in clinical settings and epidemiological studies. Here, we investigate odor identification as a supportive diagnostic tool for Parkinson's disease and estimate the performance of odor subsets to allow a more rapid testing of olfactory impairment. Methodology/Principal Findings Odor identification was assessed with 16 Sniffin' sticks in 148 Parkinson patients and 148 healthy controls. Risks of olfactory impairment were estimated with proportional odds models. Random forests were applied to classify Parkinson and non-Parkinson patients. Parkinson patients were rarely normosmic (identification of more than 12 odors; 16.8%) and identified on average seven odors whereas the reference group identified 12 odors and showed a higher prevalence of normosmy (31.1%). Parkinson patients with rigidity dominance had a twofold greater prevalence of olfactory impairment. Disease severity was associated with impairment of odor identification (per score point of the Hoehn and Yahr rating OR 1.87, 95% CI 1.26–2.77). Age-related impairment of olfaction showed a steeper gradient in Parkinson patients. Coffee, peppermint, and anise showed the largest difference in odor identification between Parkinson patients and controls. Random forests estimated a misclassification rate of 22.4% when comparing Parkinson patients with healthy controls using all 16 odors. A similar rate (23.8%) was observed when only the three aforementioned odors were applied. Conclusions/Significance Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point

Serum lipid alterations in GBA-associated Parkinson's disease.

PubMed

Guedes, Leonor Correia; Chan, Robin Barry; Gomes, Marcos António; Conceição, Vasco A; Machado, Raquel Bouça; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, Joao André; Alcalay, Roy N; Ferreira, Joaquim J; Outeiro, Tiago Fleming; Miltenberger-Miltenyi, Gabriel

2017-11-01

Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation

PubMed Central

Närvä, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Huha-Pekka; Nästi, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lähdesmäki, Harri; Rao, Anjana; Lahesmaa, Ritta

2012-01-01

Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. PMID:22162396

Motivational modes and learning in Parkinson's disease.

PubMed

Foerde, Karin; Braun, Erin Kendall; Higgins, E Tory; Shohamy, Daphna

2015-08-01

Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Thiazolidinediones and Parkinson Disease: A Cohort Study.

PubMed

Connolly, John G; Bykov, Katsiaryna; Gagne, Joshua J

2015-12-01

Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Occupation and risk of parkinsonism: a multicenter case-control study.

PubMed

Tanner, Caroline M; Ross, G Webster; Jewell, Sarah A; Hauser, Robert A; Jankovic, Joseph; Factor, Stewart A; Bressman, Susan; Deligtisch, Amanda; Marras, Connie; Lyons, Kelly E; Bhudhikanok, Grace S; Roucoux, Diana F; Meng, Cheryl; Abbott, Robert D; Langston, J William

2009-09-01

We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. Case-control. Eight movement disorders centers in North America. Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis parkinsonism. Unexpected increased risks associated with legal, construction and extraction, or religious occupations were not maintained after adjustment for duration. Risk of parkinsonism increased with pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any of 8 pesticides mechanistically associated with experimental parkinsonism (2.20; 1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of the specific occupations, job tasks, or task-related exposures were associated with younger age at diagnosis (parkinsonism. Tobacco use was inversely associated with parkinsonism risk. The association of disease risk with pesticides support a toxicant-induced cause of parkinsonism.

Increased pulsatility index supports diagnosis of vascular parkinsonism versus idiopathic Parkinson's disease.

PubMed

Caba, L M; Ferrairó, J I T; Torres, I M; Costa, J F V; Muñoz, R B; Martin, A L

2017-12-29

The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Parkinson's Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort.

PubMed

Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T; Ben-Shlomo, Yoav; Hu, Michele T M

2015-01-01

Within Parkinson's there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Use a data-driven approach to unravel any heterogeneity in the Parkinson's phenotype in a well-characterised, population-based incidence cohort. 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Our approach identified several Parkinson's phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson's.

[Sleep disturbances in Parkinson's disease: characteristics, evaluation and therapeutic approaches].

PubMed

Faludi, Béla; Janszky, József; Komoly, Sámuel; Kovács, Norbert

2015-07-05

Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs. The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances. The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015. Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains. Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.

Parkinson's Disease

MedlinePlus

... in sexual desire or performance. Prevention Because the cause of Parkinson's is unknown, proven ways to prevent the disease also remain a mystery. However, some research has shown that caffeine — which is found in coffee, tea and cola — ...

Management of Parkinson׳s disease: Current and future pharmacotherapy.

PubMed

Kakkar, Ashish Kumar; Dahiya, Neha

2015-03-05

Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development. Copyright © 2015 Elsevier B.V. All rights reserved.

Ability to Consent to Parkinson Disease Research

MedlinePlus

... Steven Karceski, MD The ability to consent to Parkinson disease research Eran Klein, MD, PhD WHAT IS THIS ... 1 on giving consent to be part of Parkinson disease (PD) research. People with PD often want to ...

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

Responses of transgenic Arabidopsis plants and recombinant yeast cells expressing a novel durum wheat manganese superoxide dismutase TdMnSOD to various abiotic stresses.

PubMed

Kaouthar, Feki; Ameny, Farhat-Khemakhem; Yosra, Kamoun; Walid, Saibi; Ali, Gargouri; Faiçal, Brini

2016-07-01

In plant cells, the manganese superoxide dismutase (Mn-SOD) plays an elusive role in the response to oxidative stress. In this study, we describe the isolation and functional characterization of a novel Mn-SOD from durum wheat (Triticum turgidum L. subsp. Durum), named TdMnSOD. Molecular phylogeny analysis showed that the durum TdMnSOD exhibited high amino acids sequence identity with other Mn-SOD plants. The three-dimensional structure showed that TdMnSOD forms a homotetramer and each subunit is composed of a predominantly α-helical N-terminal domain and a mixed α/β C-terminal domain. TdMnSOD gene expression analysis showed that this gene was induced by various abiotic stresses in durum wheat. The expression of TdMnSOD enhances tolerance of the transformed yeast cells to salt, osmotic, cold and H2O2-induced oxidative stresses. Moreover, the analysis of TdMnSOD transgenic Arabidopsis plants subjected to different environmental stresses revealed low H2O2 and high proline levels as compared to the wild-type plants. Compared with the non-transformed plants, an increase in the total SOD and two other antioxidant enzyme activities including catalase (CAT) and peroxidases (POD) was observed in the three transgenic lines subjected to abiotic stress. Taken together, these data provide evidence for the involvement of durum wheat TdMnSOD in tolerance to multiple abiotic stresses in crop plants. Copyright © 2016 Elsevier GmbH. All rights reserved.

[The Competence Network Parkinson (CNP)].

PubMed

Oertel, Wolfgang H; Deuschl, Guenther; Eggert, Karla

2016-04-01

The Competence Network Parkinson (CNP) is a research infrastructure for disease-oriented translational and clinical research in the field of Parkinson syndromes (PS). It was initiated in 1999 and funded until 2008 by the German Ministry for Education and Research (BMBF). The CNP created a highly frequented website with information on PS for the general public and for experts. The CNP designed and established one of the first electronic internet-based data entry systems (secuTrial®) - fulfilling the legal standards of data safety and security - a material bank for genetic research on Parkinson's disease (PD), implemented and investigated new methods for early diagnosis of PD and related atypical PS including in vivo dopamine transporter imaging (DAT SPECT), established the German Parkinson Study Group (GPS-Pharma) with 40 certified trial centres for pharmacotherapeutical trials and the German interdisciplinary Parkinson Study Group (neurology and neurosurgery) for deep brain stimulation (GPS-DBS), and carried out several pharmacoeconomic and health care studies on PD in Germany. Sustainability of the infrastructure CNP has in part been achieved in form of the GPS-Pharma and the GPS-DBS, as well as in the German Study Group on REM Sleep Behaviour Disorder (RBD), a prodromal phase of PD. Part of the CNP activities, such as genetic research and research on cohorts of PD patients, have been incorporated into the German Center for Neurodegenerative Disorders (DZNE). Furthermore, topics such as health care research are funded within projects of the EU research program. The article describes problems in setting up a competence network from scratch and contains recommendations how to avoid them in the future.

The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

PubMed Central

Goetz, Christopher G.

2011-01-01

Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

[Metronome therapy in patients with Parkinson disease].

PubMed

Enzensberger, W; Oberländer, U; Stecker, K

1997-12-01

We studied 10 patients with Parkinson's disease and 12 patients with Parkinson-plus-syndrome, trying to improve patients' gait by application of various external rhythmic stimuli, including metronome stimulation (96 beats per minute = middle andante). The test course of the patients was 4 x 10 meters and 3 U-turns. The patients' gait quality under stimulation was compared with their free walk (velocity, number of steps, number of freezing episodes). Metronome stimulation significantly reduced the time and number of steps needed for the test course and also diminished the number of freezing episodes. March music stimulation was less effective and tactile stimulation (rhythmically tapping on the patient's shoulder) even produced negative results. The positive effect of metronome stimulation was also found, when the tests were not performed inside the hospital building, but outside in the hospital parc. Metronome stimulation was comparably effective in both patient sub-groups examined in this study (M. Parkinson, Parkinson-plus-syndrome) and seems to be an important additional help in the treatment of these patients. Electronical metronomes are not expensive, easy in handling, and portable. A theoretical explanation of metronome stimulation effectivity in patients with Parkinson's disease still needs to be elucidated.

Speech and swallowing disorders in Parkinson disease.

PubMed

Sapir, Shimon; Ramig, Lorraine; Fox, Cynthia

2008-06-01

To review recent research and clinical studies pertaining to the nature, diagnosis, and treatment of speech and swallowing disorders in Parkinson disease. Although some studies indicate improvement in voice and speech with dopamine therapy and deep brain stimulation of the subthalamic nucleus, others show minimal or adverse effects. Repetitive transcranial magnetic stimulation of the mouth motor cortex and injection of collagen in the vocal folds have preliminary data supporting improvement in phonation in people with Parkinson disease. Treatments focusing on vocal loudness, specifically LSVT LOUD (Lee Silverman Voice Treatment), have been effective for the treatment of speech disorders in Parkinson disease. Changes in brain activity due to LSVT LOUD provide preliminary evidence for neural plasticity. Computer-based technology makes the Lee Silverman Voice Treatment available to a large number of users. A rat model for studying neuropharmacologic effects on vocalization in Parkinson disease has been developed. New diagnostic methods of speech and swallowing are also available as the result of recent studies. Speech rehabilitation with the LSVT LOUD is highly efficacious and scientifically tested. There is a need for more studies to improve understanding, diagnosis, prevention, and treatment of speech and swallowing disorders in Parkinson disease.

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

New interpretation of the Gran Dolina-TD6 bearing Homo antecessor deposits through sedimentological analysis

PubMed Central

Campaña, I.; Pérez-González, A.; Benito-Calvo, A.; Rosell, J.; Blasco, R.; de Castro, J. M. Bermúdez; Carbonell, E.; Arsuaga, J. L.

2016-01-01

Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments. This sequence contains the TD6 stratigraphic unit, whose records include around 170 hominin bones that have allowed the definition of a new species, Homo antecessor. This fossil accumulation was studied as a single assemblage and interpreted as a succession of several human home bases. We propose a complete stratigraphic context and sedimentological interpretation for TD6, analyzing the relationships between the sedimentary facies, the clasts and archaeo-palaeontological remains. The TD6 unit has been divided into three sub-units and 13 layers. Nine sedimentary facies have been defined. Hominin remains appear related to three different sedimentary facies: debris flow facies, channel facies and floodplain facies. They show three kinds of distribution: first a group of scattered fossils, then a group with layers of fossils in fluvial facies, and third a group with a layer of fossils in mixed fluvial and gravity flow facies. The results of this work suggest that some of these hominin remains accumulated in the cave by geological processes, coming from the adjacent slope above the cave or the cave entry, as the palaeogeography and sedimentary characteristics of these allochthonous facies suggest. PMID:27713562

Four Cases of Parkinson Disease Diagnosed During the Postpartum Period.

PubMed

Maltête, David; Grangeon, Lou; Le Goff, Floriane; Ozel, Gulden; Fetter, Damien; Ahtoy, Patrick; Temgoua, Olivier; Rouillé, Audrey; Lefaucheur, Romain

2017-07-01

There is little experience with the effect of pregnancy on Parkinson disease because the number of women with Parkinson disease who are of childbearing age is small. We report four cases beginning during the postpartum period and discuss the potential contribution of different factors that may influence the occurrence of Parkinson disease in this time period. Four women aged 29-35 years developed arm tremor, shoulder pain, dizziness, or decreased dexterity of the hand in the first few days or months after childbirth. They were initially diagnosed with postpartum depression or psychogenic parkinsonism. Finally, dopamine transporter imaging confirmed the diagnosis of young-onset Parkinson disease. Early-onset Parkinson disease may present in postpartum women. In women with atypical motor symptoms in addition to depression, this diagnosis should be considered.

Isolation and molecular characterization of a novel WIN1/SHN1 ethylene-responsive transcription factor TdSHN1 from durum wheat (Triticum turgidum. L. subsp. durum).

PubMed

Djemal, Rania; Khoudi, Habib

2015-11-01

Over the last decade, APETALA2/Ethylene Responsive Factor (AP2/ERF) proteins have become the subject of intensive research activity due to their involvement in a variety of biological processes. This research led to the identification of AP2/ERF genes in many species; however, little is known about these genes in durum wheat, one of the most important cereal crops in the world. In this study, a new member of the AP2/ERF transcription factor family, designated TdSHN1, was isolated from durum wheat using thermal asymetric interlaced PCR (TAIL-PCR) method. Protein sequence analysis showed that TdSHN1 contained an AP2/ERF domain of 63 amino acids and a putative nuclear localization signal (NLS). Phylogenetic analysis showed that TdSHN1 belongs to a group Va protein in the ERF subfamily which contains the Arabidopsis ERF proteins (SHN1, SHN2, and SHN3). Expression of TdSHN1 was strongly induced by salt, drought, abscisic acid (ABA), and cold. In planta, TdSHN1 protein was able to activate the transcription of GUS reporter gene driven by the GCC box and DRE element sequences. In addition, TdSHN1 was targeted to the nucleus when transiently expressed in tobacco epidermal cells. In transgenic yeast, overexpression of TdSHN1 increased tolerance to multiple abiotic stresses. Taken together, the results showed that TdSHN1 encodes an abiotic stress-inducible, transcription factor which confers abiotic stress tolerance in yeast. TdSHN1 is therefore a promising candidate for improvement of biotic and abiotic stress tolerance in wheat as well as other crops.

A randomized controlled trial [corrected] administration of tetanus toxoid (TT) versus tetanus and reduced diphtheria (Td) in pregnant women.

PubMed

Salama, Maha M; Hady, Osama A W; Ashour, Wael; Mostafa, Amal; El Alkamy, Sahar; El Sayed, Nehad; El Yazeed, Remon Abu

2009-07-01

The present study was designed as a randomized clinical trial to compare the immunogenicity, reactogenicity, and efficacy of tetanus toxoid (TT) and the combined tetanus and reduced diphtheria (Td) in pregnant women in four rural communities in Egypt. The pregnant women in each four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured by the Egyptian Company for Biological Products & Vaccines (VACSERA) in Egypt. A total of 131 pregnant women were enrolled during the time of antenatal care visit (at 20 weeks gestational age of pregnancy) in one of four health units in Abu Homos district, Beheira Governorate, Egypt. Unimmunized women received two random doses of either TT or Td 8 weeks apart during their pregnancy. Outpatient follow-up for adverse reactions occurred at the third day after each vaccine dose as either local effects such as pain, redness, and swelling or systematic effects such as fever, malaise, and headache or body aches which was served as primary safety endpoint. Blood was collected three times from each woman for determination of antibody titer against tetanus and diphtheria by using enzyme-linked immunosorbent assay technique. The first sample was collected immediately before the first dose, the second before the second dose, and the third sample 1 week after delivery. Active surveillance home visits to all study participants were done twice: the first home visit during the first week after delivery and the second 1 month after labor to report the health status of the mother and the baby. A total of 122 pregnant women received two ordinary doses with interdose intervals within the allowable range and three blood samples were collected in each protocol analysis (62 in the TT group and 60 in the Td group). There was no statistically significant difference between groups in the percentage of reporting a primary safety endpoint (fever, malaise, body ache, headache) or local reactions at the site of injection as redness

Parkinson's Disease Research at NIH | NIH MedlinePlus the Magazine

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Understanding Parkinson Disease: A Complex and Multifaceted Illness.

PubMed

Gopalakrishna, Apoorva; Alexander, Sheila A

2015-12-01

Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

NIH Research: Advances in Parkinson's Disease Research

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Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

PubMed

Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

2018-02-01

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

PubMed

Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

2010-01-01

Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

Young-Onset Parkinson's

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Diagnosis (Parkinson's Disease)

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Stages of Parkinson's

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Living with Parkinson's

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Effects of parkinsonism on health status in welding exposed workers.

PubMed

Harris, Rachel C; Lundin, Jessica I; Criswell, Susan R; Hobson, Angela; Swisher, Laura M; Evanoff, Bradley A; Checkoway, Harvey; Racette, Brad A

2011-11-01

Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was ≥15. All subjects completed a Parkinson's disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL's). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mortalin inhibition in experimental Parkinson's disease.

PubMed

Chiasserini, Davide; Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Susta, Federica; Orvietani, Pier Luigi; Koya, Keizo; Binaglia, Luciano; Calabresi, Paolo

2011-08-01

Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6-hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT-077, a rhodamine-123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham-operated, and 6-hydroxydopamine-denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6-hydroxydopamine-treated rats in comparison with sham-operated animals. MKT-077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT-077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease. Copyright © 2011 Movement Disorder Society.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

PubMed

Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

Parkinson's disease and periodontitis - the missing link? A review.

PubMed

Kaur, Tejaswani; Uppoor, Ashita; Naik, Dilip

2016-12-01

In this article an attempt has been made to postulate a possible link between Parkinson's disease and periodontal disease. Various systemic diseases such as cardiac disease, diabetes, renal diseases, low birth weight and Alzheimer's disease have been proposed to be linked with periodontal disease on the basis of systemic inflammation. Parkinson's disease is a chronic progressive neurodegenerative disorder with multifactorial aetiology. Until now, periodontal disease and Parkinson's disease has been linked only on the basis of poor motor and cognitive control in Parkinson's patient which leads to poor oral health maintenance. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of Parkinson's disease. Also, recently, systemic inflammation has been suggested as one of the contributing factors for neurodegeneration. Dental and medical literature especially those dealing with neurosciences were selected which highlighted the link between systemic inflammation and infection. So far there is no direct evidence implicating an effect of periodontitis in the pathogenesis of Parkinson's disease. To clarify this link, studies on population based case-control or cohort design are needed. This would be especially significant in the present era where there is paucity for preventive measures as far as a cognitive disorder such as Parkinson's disease is concerned. We cannot cure Parkinson's disease, but if in future this missing link is established, an attempt can be made to prevent it by tackling one of its possible contributors (periodontitis) for systemic inflammation by simple preventive oral hygiene measures. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

TdERF1, an ethylene response factor associated with dehydration responses in durum wheat (Triticum turgidum L. subsp. durum).

PubMed

Makhloufi, Emna; Yousfi, Fatma-Ezzahra; Pirrello, Julien; Bernadac, Anne; Ghorbel, Abdelwahed; Bouzayen, Mondher

2015-01-01

Water deficit and increasing salinization reduce productivity of wheat, the leading crop for human diet. While the complete genome sequence of this crop has not been deciphered, a BAC library screening allowed the isolation of TdERF1, the first ethylene response factor gene from durum wheat. This gene is putatively involved in mediating salt stress tolerance and its characterization provides clues toward understanding the mechanisms underlying the adaptation/tolerance of durum wheat to suboptimal growth conditions. TdERF1 expression is differentially induced by high salt treatment in 2 durum wheat varieties, the salt-tolerant Grecale (GR) and the salt-sensitive Om Rabiaa (OR). To further extend these findings, we show here that the expression of this ERF is correlated with physiological parameters, such as the accumulation of osmo-regulators and membrane integrity, that discriminate between the 2 contrasted wheat genotypes. The data confirm that GR and OR are 2 contrasted wheat genotypes with regard to salt-stress and show that TdERF1 is also induced by water stress with an expression pattern clearly discriminating between the 2 genotypes. These findings suggest that TdERF1 might be involved in responses to salt and water stress providing a potential genetic marker discriminating between tolerant and sensitive wheat varieties.

Correlates of constipation in people with Parkinson's.

PubMed

Gage, H; Kaye, J; Kimber, A; Storey, L; Egan, M; Qiao, Y; Trend, P

2011-02-01

To investigate clinical, demographic and dietary factors associated with constipation in a sample of community dwelling people with Parkinson's disease, recruited through a specialist outpatient clinic. Partners/carers provided a convenience control group. Participants completed a baseline questionnaire (background information, diet and exercise, activities of daily living: mobility and manual dexterity, health-related quality of life (SF-12), stool frequency and characteristics, extent of concern due to constipation, laxative taking), and a four-week stool diary. The Rome criterion was used to determine constipation status. Multiple regression methods were used to explore the correlates of constipation. Baseline data were provided by 121 people with Parkinson's, (54 controls), of whom 73% (25%) met the Rome criterion. Prospective diary data from 106 people with Parkinson's (43 controls) showed lower proportions: 35% (7%) meeting the Rome criterion. Among all study subjects, i.e. Parkinson's patients and controls taken together, the presence of constipation is predicted by having Parkinson's disease (p = .003; odds ratio 4.80, 95% CI 1.64-14.04) and mobility score (p = .04; odds ratio 1.15, 95% CI 1.01-1.31), but not by dietary factors. Amongst people with Parkinson's constipation is predicted by number of medications (p = .027). Laxative taking masks constipation, and is significantly associated with wearing protection against bowel incontinence (p = .009; odds ratio 4.80, 95% CI: 1.48-15.52). Constipation is disease-related, not a lifestyle factor. More research is needed on optimal management and laxative use. Copyright © 2010 Elsevier Ltd. All rights reserved.

Parkinson's disease and α-synuclein expression.

PubMed

Devine, Michael J; Gwinn, Katrina; Singleton, Andrew; Hardy, John

2011-10-01

Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. α-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of α-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of α-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. Copyright © 2011 Movement Disorder Society.

Quantifying gait patterns in Parkinson's disease

NASA Astrophysics Data System (ADS)

Romero, Mónica; Atehortúa, Angélica; Romero, Eduardo

2017-11-01

Parkinson's disease (PD) is constituted by a set of motor symptoms, namely tremor, rigidity, and bradykinesia, which are usually described but not quantified. This work proposes an objective characterization of PD gait patterns by approximating the single stance phase a single grounded pendulum. This model estimates the force generated by the gait during the single support from gait data. This force describes the motion pattern for different stages of the disease. The model was validated using recorded videos of 8 young control subjects, 10 old control subjects and 10 subjects with Parkinson's disease in different stages. The estimated force showed differences among stages of Parkinson disease, observing a decrease of the estimated force for the advanced stages of this illness.

Decreased β-phenylethylamine in CSF in Parkinson's disease

PubMed Central

Zhou, G.; Shoji, H.; Yamada, S.; Matsuishi, T.

1997-01-01

OBJECTIVE—To determine the concentrations of β-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrations of PEA in patients with Parkinson's disease.

 PMID:9416810

TD-CI simulation of the electronic optical response of molecules in intense fields II: comparison of DFT functionals and EOM-CCSD.

PubMed

Sonk, Jason A; Schlegel, H Bernhard

2011-10-27

Time-dependent configuration interaction (TD-CI) simulations can be used to simulate molecules in intense laser fields. TD-CI calculations use the excitation energies and transition dipoles calculated in the absence of a field. The EOM-CCSD method provides a good estimate of the field-free excited states but is rather expensive. Linear-response time-dependent density functional theory (TD-DFT) is an inexpensive alternative for computing the field-free excitation energies and transition dipoles needed for TD-CI simulations. Linear-response TD-DFT calculations were carried out with standard functionals (B3LYP, BH&HLYP, HSE2PBE (HSE03), BLYP, PBE, PW91, and TPSS) and long-range corrected functionals (LC-ωPBE, ωB97XD, CAM-B3LYP, LC-BLYP, LC-PBE, LC-PW91, and LC-TPSS). These calculations used the 6-31G(d,p) basis set augmented with three sets of diffuse sp functions on each heavy atom. Butadiene was employed as a test case, and 500 excited states were calculated with each functional. Standard functionals yield average excitation energies that are significantly lower than the EOM-CC, while long-range corrected functionals tend to produce average excitation energies slightly higher. Long-range corrected functionals also yield transition dipoles that are somewhat larger than EOM-CC on average. The TD-CI simulations were carried out with a three-cycle Gaussian pulse (ω = 0.06 au, 760 nm) with intensities up to 1.26 × 10(14) W cm(-2) directed along the vector connecting the end carbons. The nonlinear response as indicated by the residual populations of the excited states after the pulse is far too large with standard functionals, primarily because the excitation energies are too low. The LC-ωPBE, LC-PBE, LC-PW91, and LC-TPSS long-range corrected functionals produce responses comparable to EOM-CC.

Studying breaking of inverted emulsions with thermolysis purification TD600

NASA Astrophysics Data System (ADS)

Tarasova, G. I.; Shevaga, O. N.; Grachyova, E. O.

2018-03-01

Currently, emulsions are used in many branches of industry and agriculture. It explains significant attention paid to issues in production, stabilization and breaking of emulsion. Besides, producing steady emulsions is of importance in many processes; the reverse problem, that of demulsification, is important as well in oil production and treatment of oil emulsion waste water. This paper studies the breaking (demulsification) of inverted emulsions with the help of thermolysis purification TD600, produced by thermal modification of purification, a large-scale waste of the sugar industry.

Autobiographical memory in Parkinson's disease: a retrieval deficit.

PubMed

Souchay, Celine; Smith, Sarah Jane

2013-09-01

This study examined the effects of providing cues to facilitate autobiographical memory retrieval in Parkinson's disease. Previous findings have shown that individuals with Parkinson's disease retrieve fewer specific autobiographical memories than older adult controls. These findings are clinically significant since the quality of autobiographical memory is linked to identity and sense of self. In the current study, 16 older adults with Parkinson's disease without dementia and 16 matched older adult controls were given 3 min in which to recall autobiographical memories associated with five different time periods and to give each memory a short title. Participants were later asked to retrieve the memories in three phases: firstly in a free recall phase; secondly in response to general cues (time periods) and finally in response to specific cues (the short titles previously given). The number of memories and the quality of the memory (general or specific) was recorded in each condition. Compared with matched older adult controls, the Parkinson's disease group was impaired in retrieving the memories that they had previously given in the free recall phase and in response to general cues. The performance of the group with Parkinson's disease was only equivalent to the older adults when they retrieved memories in response to self-generated cues. The findings are discussed in relation to theories of autobiographical memory and the neuropsychology of Parkinson's disease. © 2013 The British Psychological Society.

Genetic influences on cognitive decline in Parkinson's disease

PubMed Central

Morley, J.F.; Xie, S.X.; Hurtig, H.I.; Stern, M.B.; Colcher, A.; Horn, S.; Dahodwala, N.; Duda, J.E.; Weintraub, D.; Chen-Plotkin, A.S.; Van Deerlin, V.; Falcone, D.; Siderowf, A.

2012-01-01

Background The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. Methods We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. Results The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. Conclusion These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients. PMID:22344634

Accuracy of Td-DFT in the Ultraviolet and Circular Dichroism Spectra of Deoxyguanosine and Uridine.

PubMed

Miyahara, Tomoo; Nakatsuji, Hiroshi

2018-01-11

Accuracy of the time-dependent density functional theory (Td-DFT) was examined for the ultraviolet (UV) and circular dichroism (CD) spectra of deoxyguanosine (dG) and uridine, using 11 different DFT functionals and two different basis sets. The Td-DFT results of the UV and CD spectra were strongly dependent on the functionals used. The basis-set dependence was observed only for the CD spectral calculations. For the UV spectra, the B3LYP and PBE0 functionals gave relatively good results. For the CD spectra, the B3LYP and PBE0 with 6-311G(d,p) basis gave relatively permissible result only for dG. The results of other functionals were difficult to be used for the studies of the UV and CD spectra, though the symmetry adapted cluster-configuration interaction (SAC-CI) method reproduced well the experimental spectra of these molecules. To obtain valuable information from the theoretical calculations of the UV and CD spectra, the theoretical tool must be able to reproduce correctly both of the intensities and peak positions of the UV and CD spectra. Then, we can analyze the reasons of the changes of the intensity and/or the peak position to clarify the chemistry involved. It is difficult to recommend Td-DFT as such tools of science, at least from the examinations using dG and uridine.

Physical therapy and occupational therapy in Parkinson's disease.

PubMed

Radder, Danique L M; Sturkenboom, Ingrid H; van Nimwegen, Marlies; Keus, Samyra H; Bloem, Bastiaan R; de Vries, Nienke M

2017-10-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies

Parkinson disease. Unravelling the nonmotor mysteries of Parkinson disease.

PubMed

Chaudhuri, K Ray; Sauerbier, Anna

2016-01-01

Parkinson disease (PD) is now regarded as a mixed motor, nonmotor and multiorgan disorder rather than a pure movement disorder. Nonmotor symptoms (NMS) have underpinned this conceptual change, and new criteria for clinical and prodromal diagnosis of PD, incorporating a range of NMS, have recently been published.

Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

PubMed

Rana, Abdul Qayyum; Qureshi, Abdul Rehman M; Rahman, Labiba; Jesudasan, Ajantha; Hafez, Kevin K; Rana, Mohammad A

2016-01-01

The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

PubMed Central

Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2008-01-01

Background Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV). Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting. PMID:18419829

Gene Therapy for Parkinson's Disease

PubMed Central

Denyer, Rachel; Douglas, Michael R.

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field. PMID:22619738

Gene therapy for Parkinson's disease.

PubMed

Denyer, Rachel; Douglas, Michael R

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

Emittance of TD-NiCr after simulated reentry

NASA Technical Reports Server (NTRS)

Clark, R. K.; Dicus, D. L.; Lisagor, W. B.

1978-01-01

The effects of simulated reentry heating on the emittance of TD-NiCr were investigated. Groups of specimens with three different preconditioning treatments were exposed to 6, 24, and 30 half-hour simulated reentry exposure cycles in a supersonic arc tunnel at each of three conditions intended to produce surface temperatures of 1255, 1365, and 1475 K. Emittance was determined at 1300 K on specimens which were preconditioned only and specimens after completion of reentry simulation exposure. Oxide morphology and chemistry were studied by scanning electron microscopy and X-ray diffraction analysis. A consistent relationship was established between oxide morphology and total normal emittance. Specimens with coarser textured oxides tended to have lower emittances than specimens with finer textured oxides.

Parkinson Disease and Dementia.

PubMed

Garcia-Ptacek, Sara; Kramberger, Milica G

2016-09-01

Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. © The Author(s) 2016.

Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

PubMed

Müller, Jan; Myers, Jonathan

2018-01-01

Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

Parkinson's Disease: Leucine-Rich Repeat Kinase 2 and Autophagy, Intimate Enemies

PubMed Central

Bravo-San Pedro, José M.; Gómez-Sánchez, Rubén; Pizarro-Estrella, Elisa; Niso-Santano, Mireia; González-Polo, Rosa A.; Fuentes Rodríguez, José M.

2012-01-01

Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology. PMID:22970411

Parkinson Disease: Treating Symptoms Unrelated to Muscle Movement

MedlinePlus

... Evidence-based Guideline for PATIENTS and their FAMILIES PARKINSON DISEASE: TREATING SYMPTOMS UNRELATED TO MUSCLE MOVEMENT This fact sheet may help you understand which therapies help Parkinson disease (PD) symptoms unrelated to muscle movement. Neurologists from ...

POLG1-related levodopa-responsive parkinsonism.

PubMed

Miguel, Rita; Gago, Miguel Fernandes; Martins, João; Barros, Pedro; Vale, José; Rosas, Maria José

2014-11-01

Parkinsonian features have been described in patients with POLG1 mutations. Notwithstanding, the clinical expression has been revealed heterogeneous and the response to dopaminergic treatment has been document in few cases. We aim to describe the longitudinal clinical features and the treatment response of three unrelated patients with neurodegenerative parkinsonism, preceded by PEO and SANDO syndromes, who harbor POLG1 mutations, including two novel mutations. It was documented a sustained response to levodopa, at 3 and 8 years of follow-up of parkinsonian syndrome, and reduced striatal dopamine uptake. We review the genotypic and phenotypic spectrum of POLG1-related parkinsonism. Our observations stimulate the debate around the role of mitochondrial DNA defects in the pathogenesis of neurodegenerative parkinsonism. Copyright © 2014 Elsevier B.V. All rights reserved.

Design of Servo Scheme and Drive Electronics for the Integrated Electrohydraulic Actuation System of RLV-TD

NASA Astrophysics Data System (ADS)

Kurian, Priya C.; Gopinath, Anish; Shinoy, K. S.; Santhi, P.; Sundaramoorthy, K.; Sebastian, Baby; Jaya, B.; Namboodiripad, M. N.; Mookiah, T.

2017-12-01

Reusable Launch Vehicle-Technology Demonstrator (RLV-TD) is a system which has the ability to carry a payload from the earth's surface to the outer space more than once. The control actuation forms the major component of the control system and it actuates the control surfaces of the RLV-TD based on the control commands. Eight electro hydraulic actuators were used in RLV-TD for vectoring the control surfaces about their axes. A centralised Hydraulic Power Generating Unit (HPU) was used for powering the eight actuators located in two stages. The actuation system had to work for the longest ever duration of about 850 s for an Indian launch vehicle. High bandwidth requirement from autopilot was met by the servo design using the nonlinear mathematical model. Single Control Electronics which drive four electrohydraulic actuators was developed for each stage. High power electronics with soft start scheme was realized for driving the BLDC motor which is the prime mover for hydraulic pump. Many challenges arose due to single HPU for two stages, uncertainty of aero load, higher bandwidth requirements etc. and provisions were incorporated in the design to successfully overcome them. This paper describes the servo design and control electronics architecture of control actuation system.

The relationship between anisotropic magnetoresistance and topology of Fermi surface in Td-MoTe2 crystal

NASA Astrophysics Data System (ADS)

Lv, Yang-Yang; Li, Xiao; Pang, Bin; Cao, Lin; Lin, Dajun; Zhang, Bin-Bin; Yao, Shu-Hua; Chen, Y. B.; Zhou, Jian; Dong, Song-Tao; Zhang, Shan-Tao; Lu, Ming-Hui; Chen, Yan-Feng

2017-07-01

Layered transition-metal dichalcogenides have been recently attracted a lot of attention because of their unique physical properties, such as extremely large and anisotropic magnetoresistance (MR) in WTe2. In this work, we observed the abnormally anisotropic MR on Td-MoTe2 crystal that is strongly dependent on the temperature, as well as the orientations of both magnetic field B and electric field E with respect to crystallographic axes of Td-MoTe2. When E//a-axis and B//c-axis, MR is parabolically dependent on B and is as high as 520% under 9 T and 2 K conditions; the MR is quasi-linearly dependent on B when E//a-axis and B//b-axis (E//b-axis and B//c-axis), and the corresponding MR is only 130% (220%); MR is initially parabolically dependent on B, then linearly on B, and finally shows a saturate trend under E//B//a-axis (or E//B//b-axis) conditions, and the MR is about 16% (30%). These anisotropic MR behaviors can be qualitatively explained by the features of the Fermi surface of Td-MoTe2. This work may demonstrate the rich anisotropic physical behavior in layered transition-metal dichalcognides.

Copper and Copper Proteins in Parkinson's Disease

PubMed Central

Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

2014-01-01

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

Daytime Napping, Nighttime Sleeping, and Parkinson Disease

PubMed Central

Gao, Jianjun; Huang, Xuemei; Park, Yikyung; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2011-01-01

Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996–1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995–1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease. PMID:21402730

Effects of Parkinsonism on Health Status in Welding Exposed Workers

PubMed Central

Harris, Rachel C.; Lundin, Jessica I.; Criswell, Susan R.; Hobson, Angela; Swisher, Laura M.; Evanoff, Bradley A.; Checkoway, Harvey; Racette, Brad A.

2011-01-01

Background Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Methods Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was >15. All subjects completed a Parkinson’s disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Results Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL’s). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Conclusion Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. PMID:21724446

New foot remains from the Gran Dolina-TD6 Early Pleistocene site (Sierra de Atapuerca, Burgos, Spain).

PubMed

Pablos, Adrián; Lorenzo, Carlos; Martínez, Ignacio; Bermúdez de Castro, José María; Martinón-Torres, María; Carbonell, Eudald; Arsuaga, Juan Luis

2012-10-01

This paper presents and describes new foot fossils from the species Homo antecessor, found in level TD6 of the site of Gran Dolina (Sierra de Atapuerca, Burgos, Spain). These new fossils consist of an almost complete left talus (ATD6-95) and the proximal three-quarters of a right fourth metatarsal (ATD6-124). The talus ATD6-95 is tentatively assigned to Hominin 10 of the TD6 sample, an adult male specimen with which the second metatarsal ATD6-70+107 (already published) is also tentatively associated. Analysis of these fossils and other postcranial remains has made possible to estimate a stature similar to those of the specimens from the Middle Pleistocene site of Sima de los Huesos (Sierra de Atapuerca, Burgos, Spain). The morphology of the TD6 metatarsals does not differ significantly from that of modern humans, Neanderthals and the specimens from Sima de los Huesos. Talus ATD6-95, however, differs from the rest of the comparative samples in being long and high, having a long and wide trochlea, and displaying a proportionally short neck. Copyright © 2012 Elsevier Ltd. All rights reserved.

Replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus and isolation of a td mutant from duck-adapted PR-RSV-C.

PubMed

Geryk, J; Mazo, A; Svoboda, J; Hlozánek, I

1980-01-01

The replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus subgroup C was studied using roller cultures. Under such conditions, 10(5)--10(6) infectous units of virus per 0.2 ml were produced, as revealed in both the reverse transcriptase and 16Q complementation tests. A new td daPR-RSV-C mutant was isolated from duck-adapted PR-RSV-C. This mutant replicated in roller cultures with equal efficiency as the original td PR-RSV-C. It was verified that td daPR-RSV-C does not transform chicken fibroblasts, is not oncogenic for 3-week-old chickens and has subgroup C host-range specificity. Both td mutants replicate in duck cells and reach the same titres.

Tardive dyskinesia

MedlinePlus

... as levodopa Antiseizure drugs such as phenobarbital and phenytoin Symptoms Symptoms of TD may include: Facial grimacing ... ncbi.nlm.nih.gov/pubmed/23897874 . Jankovic J. Parkinson disease and other movement disorders. In: Daroff RB, ...

Excessive daytime sleepiness in Parkinson disease: a SPECT study.

PubMed

Matsui, Hideaki; Nishinaka, Kazuto; Oda, Masaya; Hara, Narihiro; Komatsu, Kenichi; Kubori, Tamotsu; Udaka, Fukashi

2006-07-01

The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. Clinical study. Sumitomo Hospital. Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Rasagiline. Parkinson's disease: a simple me-too.

PubMed

2006-12-01

In Parkinson's disease, rasagiline, either alone (in early stage disease) or combined with levodopa, provides nothing new in terms of efficacy or tolerability. It is better to continue using one of the many anti-parkinson drugs with which we have more experience rather than expose patients to a new drug which offers no advantages.

Update in therapeutic strategies for Parkinson's disease.

PubMed

Kulisevsky, Jaime; Oliveira, Lais; Fox, Susan H

2018-05-08

To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

Is PIGD a legitimate motor subtype in Parkinson disease?

PubMed

Kotagal, Vikas

2016-06-01

Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients.

PubMed

Stokholm, Morten Gersel; Danielsen, Erik Hvid; Hamilton-Dutoit, Stephen Jacques; Borghammer, Per

2016-06-01

It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase. We used the Danish National Pathology Registry to identify archived paraffin-embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks). We employed 2 different immunohistochemistry techniques visualizing aggregated α-synuclein and phosphorylated α-synuclein. Thirty-nine Parkinson disease patients contributed tissues obtained in the prodromal disease phase, whereas 18 Parkinson disease patients contributed tissues obtained solely after Parkinson diagnosis. Prodromal tissues were obtained on average 7.0 years prior to diagnosis (range = 20 years to 4 months), and postdiagnosis tissue on average 2.8 years after diagnosis (range = 2 days to 18 years). Phosphorylated α-synuclein positivity was seen in 22 of 39 (56%) prodromal Parkinson disease subjects and 30 of 67 (45%) prodromal tissue blocks. These fractions were significantly higher compared to control subjects (p = 0.0001 and p = 0.0032, respectively). In contrast, no significant difference was seen in the positivity rate between prodromal Parkinson disease patients and controls when using the aggregated α-synuclein immunohistochemistry technique. We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10 to 20 years. Ann Neurol 2016;79:940-949. © 2016 American Neurological Association.

Methamphetamine and Parkinson's Disease

PubMed Central

Granado, Noelia; Ares-Santos, Sara; Moratalla, Rosario

2013-01-01

Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. PMID:23476887

Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI).

PubMed

Nalls, Mike A; Keller, Margaux F; Hernandez, Dena G; Chen, Lan; Stone, David J; Singleton, Andrew B

2016-01-01

The Parkinson's Progression Marker Initiative is an international multicenter study whose main goal is investigating markers for Parkinson's disease (PD) progression as part of a path to a treatment for the disease. This manuscript describes the baseline genetic architecture of this study, providing not only a catalog of disease-linked variants and mutations, but also quantitative measures with which to adjust for population structure. Three hundred eighty-three newly diagnosed typical PD cases, 65 atypical PD and 178 healthy controls, from the Parkinson's Progression Marker Initiative study have been genotyped on the NeuroX or Immunochip arrays. These data are freely available to all researchers interested in pursuing PD research within the Parkinson's Progression Marker Initiative. The Parkinson's Progression Marker Initiative represents a study population with low genetic heterogeneity. We recapitulate known PD associations from large-scale genome-wide association studies and refine genetic risk score models for PD predictability (area under the curve, ∼0.74). We show the presence of six LRRK2 p.G2019S and nine GBA p.N370S mutation carriers. The Parkinson's Progression Marker Initiative study and its genetic data are useful in studies of PD biomarkers. The genetic architecture described here will be useful in the analysis of myriad biological and clinical traits within this study. © 2015 International Parkinson and Movement Disorder Society.

Current management of Parkinson's disease.

PubMed

Salawu, F; Olokoba, A; Danburam, A

2010-01-01

Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become available to improve the quality of life and physical and psychological morbidity, and its early treatment is of prime importance. This article reviews the current situation of PD. This review was based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Parkinson's disease and therapeutic advances. Only articles written in English were included.The management of PD has evolved rapidly over the last 10 years with the advent of new drugs and new classes of drugs, but the currently available treatment methods are all symptomatic ones. However, some of these may have marginal disease-modifying effects. Progress in manufacture of newer drugs has markedly improved the treatment of early PD; however, the management of advanced Parkinson's symptoms remains a challenge. Currently no treatment has been proven to slow the progression of PD. Although symptomatic therapy can provide benefit for many years, PD will eventually result in significant morbidity.

Tai Chi Exercise to Improve Non-Motor Symptoms of Parkinson's Disease.

PubMed

Nocera, Joe R; Amano, Shinichi; Vallabhajosula, Srikant; Hass, Chris J

2013-08-20

A substantial number of individuals with Parkinson's disease exhibit debilitating non-motor symptoms that decrease quality of life. To date, few treatment options exist for the non-motor symptomatology related to Parkinson's disease. The goal of this pilot investigation was to determine the effects of Tai Chi exercise on the non-motor symptomology in Parkinson's disease. Twenty-one individuals with Parkinson's disease were enrolled in a Tai Chi intervention (n=15) or a noncontact control group (n=6). Participants assigned to Tai Chi participated in 60-minute Tai Chi sessions three times per week, for 16 weeks. Pre and post measures included indices of cognitive-executive function including visuomotor tracking and attention, selective attention, working memory, inhibition, processing speed and task switching. Additionally, all participants were evaluated on the Parkinson's disease Questionnaire-39 and Tinetti's Falls Efficacy Scale. Results indicated that the Tai Chi training group had significantly better scores following the intervention than the control group on the Parkinson's disease Questionnaire-39 total score as well as the emotional well-being sub score. Trends for improvement were noted for the Tai Chi group on Digits Backwards, Tinetti's Falls Efficacy Scale, and the activities of daily living and communication sub scores of the Parkinson's disease Questionnaire-39. This research provides initial data that supports future studies to definitively establish efficacy of Tai Chi to improve non-motor features of Parkinson's disease.

Is cerebral vasomotor reactivity impaired in Parkinson disease?

PubMed

Hanby, Martha F; Panerai, Ronney B; Robinson, Thompson G; Haunton, Victoria J

2017-04-01

The ability of a blood vessel to change diameter in response to a change in carbon dioxide concentration is often referred to as vasomotor reactivity. This study aimed to determine whether vasomotor reactivity is impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls. Transcranial Doppler was used to measure cerebral blood flow velocity in the middle cerebral arteries at baseline and under hypocapnic conditions in 40 patients with idiopathic Parkinson's disease and 50 healthy controls. Vasomotor reactivity, assessed under hypocapnic conditions, is not impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls.

Doppler sonography characteristics of vertebrobasilar circulation in patients with Parkinson's disease.

PubMed

Vidović, Mirjana; Sinanović, Osman; Smajlović, Dzevdet; Burina, Adnan; Hudić, Josip

2008-08-01

The objective of the study was to analyze the doppler sonography findings of vertebrobasilar circulation (VB) in patients with Parkinson's disease. 40 patients were analyzed (25 men's and 15 women) with Parkinson's disease, average age was 61.9 years (SD=11.43), treated at the Clinic for Neurology in Tuzla. Device for doppler sonography was Multidop x 4. Doppler sonography findings of VB circulation were analyzed in order to computerized tomography (CT) findings of the brain (with or without ischemic lacunar lesions) and in order to presence of postural disturbances as one of dominant Parkinson's disease symptoms during actual hospitalization. Our results suggest that vertebrobasilar insufficiency is more frequent in patients with Parkinson's disease (no matter of type) and postural disturbances as a dominant symptom comparing to group of Parkinson's disease patients without postural disturbances. These results implicate the importance of doppler sonography findings of vertebrobasilar circulation in patients with Parkinson's disease and possibility of considering role of vertebrobasilar insufficiency in development of postural disturbances.

Office-Based Screening for Dementia in Parkinson Disease: The Montreal Parkinson Risk of Dementia Scale in 4 Longitudinal Cohorts.

PubMed

Dawson, Benjamin K; Fereshtehnejad, Seyed-Mohammad; Anang, Julius B M; Nomura, Takashi; Rios-Romenets, Silvia; Nakashima, Kenji; Gagnon, Jean-François; Postuma, Ronald B

2018-06-01

Parkinson disease dementia dramatically increases mortality rates, patient expenditures, hospitalization risk, and caregiver burden. Currently, predicting Parkinson disease dementia risk is difficult, particularly in an office-based setting, without extensive biomarker testing. To appraise the predictive validity of the Montreal Parkinson Risk of Dementia Scale, an office-based screening tool consisting of 8 items that are simply assessed. This multicenter study (Montreal, Canada; Tottori, Japan; and Parkinson Progression Markers Initiative sites) used 4 diverse Parkinson disease cohorts with a prospective 4.4-year follow-up. A total of 717 patients with Parkinson disease were recruited between May 2005 and June 2016. Of these, 607 were dementia-free at baseline and followed-up for 1 year or more and so were included. The association of individual baseline scale variables with eventual dementia risk was calculated. Participants were then randomly split into cohorts to investigate weighting and determine the scale's optimal cutoff point. Receiver operating characteristic curves were calculated and correlations with selected biomarkers were investigated. Dementia, as defined by Movement Disorder Society level I criteria. Of the 607 patients (mean [SD] age, 63.4 [10.1]; 376 men [62%]), 70 (11.5%) converted to dementia. All 8 items of the Montreal Parkinson Risk of Dementia Scale independently predicted dementia development at the 5% significance level. The annual conversion rate to dementia in the high-risk group (score, >5) was 14.9% compared with 5.8% in the intermediate group (score, 4-5) and 0.6% in the low-risk group (score, 0-3). The weighting procedure conferred no significant advantage. Overall predictive validity by the area under the receiver operating characteristic curve was 0.877 (95% CI, 0.829-0.924) across all cohorts. A cutoff of 4 or greater yielded a sensitivity of 77.1% (95% CI, 65.6-86.3) and a specificity of 87.2% (95% CI, 84.1-89.9), with a

Elective Thoracolumbar Spine Fusion Surgery in Patients with Parkinson Disease.

PubMed

Puvanesarajah, Varun; Jain, Amit; Qureshi, Rabia; Carstensen, S Evan; Tyger, Rosemarie; Hassanzadeh, Hamid

2016-12-01

Few data are available concerning clinical outcomes in patients with Parkinson disease who undergo elective thoracolumbar spine fusion surgery. The goal of this study is to elucidate complication and revision rates after posterior thoracolumbar fusion surgery in patients with Parkinson disease, with a focus on how Parkinson disease modifies these rates. The PearlDiver database (2005-2012) was queried for patients who underwent posterior approach thoracolumbar fusion from 2006 to 2011. Cohorts of patients with a previous diagnosis of Parkinson disease (n = 4816) and without (n = 280,702) were compared. Multivariate analysis that included various comorbidities and demographics was used to calculate effects of Parkinson disease on development of postoperative infection and major medical complications within 90 days and revision surgery within 1 year. For analyses, significance was set at P < 0.001. Major medical complications were observed in 545 patients (11.3%) for 90 days after the index procedure. Postoperative infection was noted in 91 patients (1.9%) within 90 days, and revision surgeries were performed in 250 patients (5.2%) within 1 year. Multivariate analysis showed that Parkinson disease was significantly associated with an increased risk for medical complications (adjusted odds ratio, 1.22; 95% confidence interval, 1.11-1.34; P < 0.001) and revision surgery (adjusted odds ratio, 1.70; 95% confidence interval, 1.49-1.93; P < 0.001), but not postoperative infection (P = 0.02). Patients with Parkinson disease are more likely to require revision surgery and have higher rates of adverse medical events postoperatively. Patients with Parkinson disease should be appropriately selected to ensure favorable clinical outcomes. Copyright © 2016. Published by Elsevier Inc.

Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease.

PubMed

Murphy, Karen E; Gysbers, Amanda M; Abbott, Sarah K; Tayebi, Nahid; Kim, Woojin S; Sidransky, Ellen; Cooper, Antony; Garner, Brett; Halliday, Glenda M

2014-03-01

Heterozygous mutations in GBA1, the gene encoding lysosomal glucocerebrosidase, are the most frequent known genetic risk factor for Parkinson's disease. Reduced glucocerebrosidase and α-synuclein accumulation are directly related in cell models of Parkinson's disease. We investigated relationships between Parkinson's disease-specific glucocerebrosidase deficits, glucocerebrosidase-related pathways, and α-synuclein levels in brain tissue from subjects with sporadic Parkinson's disease without GBA1 mutations. Brain regions with and without a Parkinson's disease-related increase in α-synuclein levels were assessed in autopsy samples from subjects with sporadic Parkinson's disease (n = 19) and age- and post-mortem delay-matched controls (n = 10). Levels of glucocerebrosidase, α-synuclein and related lysosomal and autophagic proteins were assessed by western blotting. Glucocerebrosidase enzyme activity was measured using a fluorimetric assay, and glucocerebrosidase and α-synuclein messenger RNA expression determined by quantitative polymerase chain reaction. Related sphingolipids were analysed by mass spectrometry. Multivariate statistical analyses were performed to identify differences between disease groups and regions, with non-parametric correlations used to identify relationships between variables. Glucocerebrosidase protein levels and enzyme activity were selectively reduced in the early stages of Parkinson's disease in regions with increased α-synuclein levels although limited inclusion formation, whereas GBA1 messenger RNA expression was non-selectively reduced in Parkinson's disease. The selective loss of lysosomal glucocerebrosidase was directly related to reduced lysosomal chaperone-mediated autophagy, increased α-synuclein and decreased ceramide. Glucocerebrosidase deficits in sporadic Parkinson's disease are related to the abnormal accumulation of α-synuclein and are associated with substantial alterations in lysosomal chaperone-mediated autophagy

Drugs of abuse and Parkinson's disease.

PubMed

Mursaleen, Leah R; Stamford, Jonathan A

2016-01-04

The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Conditions Related to Parkinson's

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

What Is Parkinson's Disease?

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Conditions that Mimic Parkinson's

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Foundation: For Caregivers

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Parkinson's Disease Foundation News

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... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Mirror movements in parkinsonism: evaluation of a new clinical sign

PubMed Central

Espay, A; Li, J; Johnston, L; Chen, R; Lang, A

2005-01-01

Background: Mirror movements (MM) are not widely appreciated in parkinsonism and no report has evaluated this clinical sign in detail. Objectives: To define the parkinsonian clinical features associated with MM in patients with early, asymmetric parkinsonism. Methods: Twenty seven patients with early Parkinson's disease were evaluated using a standardised videotaping protocol. MM were scored from blinded video assessment using a clinical scale that rates the amplitude, distribution, and proportion of mirroring in the less affected limb. Parkinsonian features were combined into axial and lateralised scores using related items of the Unified Parkinson's Disease Rating Scale. Results: MM were present in 24 of 27 patients. There was a significant linear correlation between the degree of asymmetry of motor deficits and MM on the less affected side. The effect of asymmetry was greater when the proportional rather than the absolute motor difference between sides was largest. Asymmetry in leg rigidity was the most important examination feature in the prediction of contralateral foot mirroring. Conclusions: MM are a clinical feature of the unaffected or less affected side in mild asymmetric parkinsonism. Their presence may be a useful clinical finding in early parkinsonism. PMID:16170075

Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

PubMed

Zokaei, Nahid; McNeill, Alisdair; Proukakis, Christos; Beavan, Michelle; Jarman, Paul; Korlipara, Prasad; Hughes, Derralynn; Mehta, Atul; Hu, Michele T M; Schapira, Anthony H V; Husain, Masud

2014-08-01

Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short

Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

ERIC Educational Resources Information Center

Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

2011-01-01

Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

▼ Safinamide for Parkinson's disease.

PubMed

2018-05-01

▼ Safinamide (Xadago - Zambon S.p.A) is a monoamine-oxidase B (MAO-B) inhibitor licensed as add-on therapy for people with idiopathic Parkinson's disease who are experiencing motor fluctuations with levodopa. 1 Currently there is no cure for Parkinson's disease and drugs are used to reduce motor symptoms and improve daily activities. 2,3 Here, we review the evidence for this MAO-B inhibitor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metabolic Imaging in Parkinson Disease.

PubMed

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

The emerging science of precision medicine and pharmacogenomics for Parkinson's disease.

PubMed

Payami, Haydeh

2017-08-01

Current therapies for Parkinson's disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials because of inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson's disease patients, when we know this premise is wrong because (1) Parkinson's disease is not a single disease, and (2) no two individuals have the same biological makeup. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson's disease reaps the benefits. Pharmacogenomics, a cornerstone of precision medicine, has already proven successful for many conditions and could also propel drug discovery and improve treatment for Parkinson's disease. To make progress in the pharmacogenomics of Parkinson's disease, we need to change course from small inconclusive candidate gene studies to large-scale rigorously planned genome-wide studies that capture the nuclear genome and the microbiome. Pharmacogenomic studies must use homogenous subtypes of Parkinson's disease or apply the brute force of statistical power to overcome heterogeneity, which will require large sample sizes achievable only via internet-based methods and electronic databases. Large-scale pharmacogenomic studies, together with biomarker discovery efforts, will yield the knowledge necessary to design clinical trials with precision to alleviate confounding by disease heterogeneity and interindividual variability in drug response, two of the major impediments to successful drug discovery and effective treatment. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Parkinson's disease in China.

PubMed

Tian, You-yong; Tang, Cui-ju; Wu, Jie; Zhou, Jun-shan

2011-02-01

Paralysis agitans was first documented in 1817 by James Parkinson, and therefore the syndrome was named Parkinson's disease (PD). In fact, as early as more than 2000 years ago, the clinical manifestations of this disease have been described in Chinese medicine classics, such as the "Huangdi Neijing (Yellow Emperor's Internal Classic)" and "Zhong Zang Jing (Hua's Zhong Zang Classic)." In recent years, especially in the past 30 years after reform and opening-up, PD has drawn a lot of attention by Chinese scholars. Although great progress in the studies of PD has been made in recent years, the gap between China and western countries still exists. In this review, we concentrate on the main progress made in epidemic characteristics, etiology, diagnosis and management of PD in China.

Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease

PubMed Central

Massey, Luke A.; Lees, Andrew J.; Brown, Peter; Day, Brian L.

2012-01-01

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as ‘slowness of initiation with progressive reduction in speed and amplitude of repetitive action’. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (−0.20°/cycle, P = 0.002). ‘Hypokinesia’, defined as <50% of control group's mean amplitude, combined with ‘absence of decrement’, defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

PubMed Central

Gwinn, Katrina; David, Karen K; Swanson-Fischer, Christine; Albin, Roger; Hillaire-Clarke, Coryse St; Sieber, Beth-Anne; Lungu, Codrin; Bowman, F DuBois; Alcalay, Roy N; Babcock, Debra; Dawson, Ted M; Dewey, Richard B; Foroud, Tatiana; German, Dwight; Huang, Xuemei; Petyuk, Vlad; Potashkin, Judith A; Saunders-Pullman, Rachel; Sutherland, Margaret; Walt, David R; West, Andrew B; Zhang, Jing; Chen-Plotkin, Alice; Scherzer, Clemens R; Vaillancourt, David E; Rosenthal, Liana S

2017-01-01

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset. PMID:28644039

Parkinson's disease: a population-based investigation of life satisfaction and employment.

PubMed

Gustafsson, Helena; Nordström, Peter; Stråhle, Stefan; Nordström, Anna

2015-01-01

To investigate relationships between individuals' socioeconomic situations and quality of life in working-aged subjects with Parkinson's disease. A population-based cohort comprising 1,432 people with Parkinson's disease and 1,135 matched controls, who responded to a questionnaire. Logistic regression analysis was performed to identify factors associated with life satisfaction and likelihood of employment. In multivariate analyses, Parkinson's disease was associated with an increased risk of dissatisfaction with life (odds ratio (OR) = 5.4, 95% confidence interval (95% CI) = 4.2-7.1) and reduced likelihood of employment (OR = 0.30, 95% CI = 0.25-0.37). Employers' support was associated with greater likelihood of employment (p < 0.001). Twenty-four percent of people with Parkinson's disease for ≥ 10 years remained employed and 6% worked full-time. People with Parkinson's disease also more frequently experienced work demands that exceeded their capacity; this factor and unemployment independently correlated with greater risk of dissatisfaction with life (both p < 0.05). People with Parkinson's disease have an increased risk of dissatisfaction with life. Employment situation is important for general life satisfaction among working-aged individuals. People with Parkinson's disease appear to find it difficult to meet the challenge of achieving a balanced employment situation.

Progressive parkinsonism in boxers.

PubMed

Friedman, J H

1989-05-01

Parkinsonism associated with boxing has attracted recent media attention, yet little has been written about it in the medical literature. This report presents a typical case with a review of the literature.

Safinamide for symptoms of Parkinson's disease.

PubMed

Müller, T

2015-11-01

Chronic and slow progression of neuronal death in Parkinson's disease is responsible for an altered neurotransmission of various biogenic amines, such as dopamine. Therefore, an individually different pronounced heterogeneity of motor and nonmotor symptoms characterizes each Parkinson's disease patient. Ideal candidates for the balance of these neurotransmitter deficits are compounds like safinamide with broad mechanisms of action such as reversible monoamine oxidase type B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and of glutamate release. Safinamide is administered one time daily with oral doses ranging from 50 to 100 mg. Safinamide was well tolerated and safe, ameliorated motor symptoms when combined with dopamine agonist only or additional levodopa in clinical trials. Safinamide is a novel instrument for the drug therapy of Parkinson's disease with better safety and tolerability particularly concerning diarrhea than inhibitors of catechol-O-methyltransferase, like entacapone, according to an indirect comparison within a meta-analysis with entacapone. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes.

PubMed

Frey, Kirk A; Petrou, Myria

2015-02-01

Dementia arising in patients with Parkinson disease or parkinsonian neurodegeneration comprises a heterogeneous neuropathology. Clinical labeling of patients with both dementia and Parkinson disease is dichotomous, depending on the temporal development of cognitive impairment and motor parkinsonism. Patients with dementia arising first (or within the first year of PD) are classified as dementia with Lewy bodies; patients with PD for more than one year before cognitive decline are classified as Parkinson disease with dementia. Despite this differential clinical classification, autopsy studies demonstrate variable admixtures of cortical synuicleinopathy, Aβ-amyloidopathy and tau neurofibrillary tangle deposition. There are no routine clinical diagnostic measures that accurately distinguish the underlying neuropathologies in individual patients. In the present paper, we review the published literature describing characteristics of fibrillary Aβ-amyloid deposition on the basis of PET radiotracer imaging in patients with Parkinson disease and in parkinsonian dementia syndromes. Although individual reports often include only small-to-modest subject numbers, there is overall suggestion that PD patients have a lower incidence of Aβ-amyloid deposition than seen amongst elderly normal subjects, and that Parkinson disease with dementia patients have a lower incidence of Aβ-amyloid deposition than do patients with dementia with Lewy bodies. These apparent features contrast the findings of Aβ-amyloid-PET imaging in normal aging and the development of Alzheimer disease, where Aβ-amyloid deposition arises asymptomatically and apparently many years before development of signs or symptoms of dementia. It is proposed that focused, prospective studies are needed to further address and understand the complex role(s) of Aβ-amyloid pathology in Parkinson disease, and that this understanding will be critical to the development of targeted disease-modifying therapy for dementia in

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

PubMed

Rissling, Ida; Körner, Yvonne; Geller, Frank; Stiasny-Kolster, Karin; Oertel, Wolfgang H; Möller, J Carsten

2005-07-01

Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. Movement disorders section at a university hospital. 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Aged monkeys as a partial model for Parkinson's disease

PubMed Central

Hurley, P.J.; Elsworth, J.D.; Whittaker, M.C.; Roth, R.H.; Redmond, D.E.

2011-01-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, eating problems, delayed initiation of movement, and poverty of movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. PMID:21620883

Predictive risk factors for chronic low back pain in Parkinson's disease.

PubMed

Ozturk, Erhan Arif; Kocer, Bilge Gonenli

2018-01-01

Although previous studies have reported that the prevalence of low back pain in Parkinson's disease was over 50% and low back pain was often classified as chronic, risk factors of chronic low back pain have not been previously investigated. The aim of this study was to determine the predictive risk factors of chronic low back pain in Parkinson's disease. One hundred and sixty-eight patients with Parkinson's disease and 179 controls were consecutively included in the study. Demographic data of the two groups and disease characteristics of Parkinson's disease patient group were recorded. Low back pain lasting for ≥3 months was evaluated as chronic. Firstly, the bivariate correlations were calculated between chronic low back pain and all possible risk factors. Then, a multivariate regression was used to evaluate the impact of the predictors of chronic low back pain. The frequency of chronic low back pain in Parkinson's disease patients and controls were 48.2% and 26.7%, respectively (p < 0.001). The predictive risk factors of chronic low back pain in Parkinson's disease were general factors including age (odds ratio = 1.053, p = 0.032) and Hospital Anxiety and Depression Scale - Depression subscore (odds ratio = 1.218, p = 0.001), and Parkinson's disease-related factors including rigidity (odds ratio = 5.109, p = 0.002) and posture item scores (odds ratio = 5.019, p = 0.0001). The chronic low back pain affects approximately half of the patients with Parkinson's disease. Prevention of depression or treatment recommendations for managing depression, close monitoring of anti- parkinsonian medication to keep motor symptoms under control, and attempts to prevent, correct or reduce abnormal posture may help reduce the frequency of chronic low back pain in Parkinson's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

ATP13A2 variability in Parkinson disease

PubMed Central

Vilariño-Güell, Carles; Soto, Alexandra I.; Lincoln, Sarah J.; Yahmed, Samia Ben; Kefi, Mounir; Heckman, Michael G.; Hulihan, Mary M.; Chai, Hua; Diehl, Nancy N.; Amouri, Rim; Rajput, Alex; Mash, Deborah C.; Dickson, Dennis W.; Middleton, Lefkos T.; Gibson, Rachel A.; Hentati, Faycal; Farrer, Matthew J.

2008-01-01

Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome, whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with non-familial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with non-familial PD and 38 healthy subjects from the US. Sequencing analysis revealed 37 new variants; seven missense, six silent and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with non-familial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or non-familial PD. PMID:19085912

Bisphenol A glucuronidation in patients with Parkinson's disease.

PubMed

Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

2017-12-01

Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (p<0.05). Moreover, no difference in Bisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

PubMed

Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

2017-08-03

To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, p<0.001, after adjustment for potential confounders), with parkinsonism and akathisia showing the greatest difference between the groups. Neuroleptic malignant syndrome, although occurring infrequently, was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication

Caring for the student with wolff-Parkinson-white syndrome.

PubMed

Prenni, Patricia G

2009-10-01

Wolff-Parkinson-White syndrome is a cardiac condition in which an extra electrical pathway within the heart causes an abnormal increase in heart rate. It affects one to three people of every 1,000 people worldwide, occurring more often in males. Diagnosis usually occurs during young adulthood, so it is important for school nurses to be familiar with the condition. Prophylactic treatments, as well as surgical intervention to permanently block the extra pathway, are options for people with Wolff-Parkinson-White syndrome. Tachycardia associated with Wolff-Parkinson-White syndrome can occur occasionally even when prophylactic treatment is administered. School nurses must know how to properly assess and treat episodes of tachycardia that may occur in the school setting. With proper education, school nurses can help provide a safe school environment for students with Wolff-Parkinson-White syndrome and promote successful academic achievement.

[Physical therapy for parkinson's disease].

PubMed

Hubert, M

2011-09-01

Parkinson's disease is a complex neurologic and progressive incapacitating disease. Parkinson's disease severely threatens the quality of live and the number of patients worldwide is expected to rise considerably in the coming decade due to aging of the population. Even with optimal medical management using drugs or neurosurgery, patients are faced with progressively increasing impairments (e.g. in speech, mental and movement related functions), and restrictions in participation (e.g. domestic life and social activities). Physical therapy is often prescribed next to medical treatment but there is a lack of uniform treatment. A systematic literature search for guidelines, systematic reviews, trials, and expert opinions lead to a better understanding. The key question: Is physiotherapy able to optimally treat the Parkinson's disease symptoms? In which way, how and on which scientific bases can the physiotherapist participate to improve autonomy and to help them living independently and avoid, as long as possible, institutionalization? This article has integrated clinical research findings to provide clinicians with an overview to physical therapist management of disorders in people with Parkinson's disease. An Evidence-Based Physical Therapy Guideline providing practice recommendations was developed by the Royal Dutch Society for Physical Therapy (KNGF). Evidence from research was supplemented with clinical expertise and patients values. Randomized clinical trials reflect specific core areas of physical therapy, that is, transfer, posture, balance, reaching and grasping, gait and physical condition. Another aspect is that of educating patients (as well as their partners and family) about the disease process and the benefits of exercise therapy. Alternative therapies can be helpful like Tai Chi, virtual games, dancing, yoga, ball games for example.

Swallowing disorders in Parkinson's disease.

PubMed

Mamolar Andrés, Sandra; Santamarina Rabanal, María Liliana; Granda Membiela, Carla María; Fernández Gutiérrez, María José; Sirgo Rodríguez, Paloma; Álvarez Marcos, César

Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO 2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Elucidation of the new generation fluorescent protein tdTomato for space related radiobiological research

NASA Astrophysics Data System (ADS)

Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther

Astronauts in space are exposed to a potentially harmful radiation field, which does not exist in its quality and quantity on earth. Radiation exposure in space can lead to delayed or acute health effects. A successful long-term space mission requires better risk estimation and development of appropriate countermeasures, therefore study of the cellular radiation response is necessary. Ionizing radiation can provoke active cellular responses (cell cycle arrest, DNA repair, apoptosis or other forms of cell type). Exposure to ionizing radiation also activates various signaling pathways in human cells. In the cellular radiation-response, two pivotal signal transduction pathways have to be comprehensively studied i.e. the p53-pathway and NF-κB-pathway. Discovery of fluorescent proteins has revolutionized biological research by making it possible to carry out functional studies in living cells and understanding complex signaling pathways. Previously the green fluorescent proteins EGFP and d2EGFP were used for signaling pathway studies. In this work the new red fluorescent protein tdTomato will be used for comprehensive investigation of NF-κB and other transcription factor activation after exposure of human cells to ionizing radiation (X-rays, heavy ions; space conditions). tdTomato has many advantages over EGFP because of its high fluorescence signals and a better signal/noise ratio in human cells. The previously constructed reporter system with d2EGFP was used to evaluate NF-kB activation after exposure to heavy ion particles of different biological effectiveness. The sensitivity threshold of this system was determined to be 2 particle traversals per cell nucleus. In the current study a more sensitive reporter assay will be constructed using a GAL4-VP16 turbo system that comprises a receptor plasmid and a reporter plasmid. This reporter assay will be designed and constructed with tdTomato and evaluation will be done with different molecular techniques.

Apathy and noradrenaline: silent partners to mild cognitive impairment in Parkinson's disease?

PubMed

Loued-Khenissi, Leyla; Preuschoff, Kerstin

2015-08-01

Mild cognitive impairment (MCI) is a comorbid factor in Parkinson's disease. The aim of this review is to examine the recent neuroimaging findings in the search for Parkinson's disease MCI (PD-MCI) biomarkers to gain insight on whether MCI and specific cognitive deficits in Parkinson's disease implicate striatal dopamine or another system. The evidence implicates a diffuse pathophysiology in PD-MCI rather than acute dopaminergic involvement. On the one hand, performance in specific cognitive domains, notably in set-shifting and learning, appears to vary with dopaminergic status. On the other hand, motivational states in Parkinson's disease along with their behavioral and physiological indices suggest a noradrenergic contribution to cognitive deficits in Parkinson's disease. Finally, Parkinson's disease's pattern of neurodegeneration offers an avenue for continued research in nigrostriatal dopamine's role in distinct behaviors, as well as the specification of dorsal and ventral striatal functions. The search for PD-MCI biomarkers has employed an array of neuroimaging techniques, but still yields divergent findings. This may be due in part to MCI's broad definition, encompassing heterogeneous cognitive domains, only some of which are affected in Parkinson's disease. Most domains falling under the MCI umbrella include fronto-dependent executive functions, whereas others, notably learning, rely on the basal ganglia. Given the deterioration of the nigrostriatal dopaminergic system in Parkinson's disease, it has been the prime target of PD-MCI investigation. By testing well defined cognitive deficits in Parkinson's disease, distinct functions can be attributed to specific neural systems, overcoming conflicting results on PD-MCI. Apart from dopamine, other systems such as the neurovascular or noradrenergic systems are affected in Parkinson's disease. These factors may be at the basis of specific facets of PD-MCI for which dopaminergic involvement has not been conclusive

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

PubMed

Suntrup, Sonja; Teismann, Inga; Bejer, Joke; Suttrup, Inga; Winkels, Martin; Mehler, David; Pantev, Christo; Dziewas, Rainer; Warnecke, Tobias

2013-03-01

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

[A core deficit in Parkinson disease?].

PubMed

Benítez-Burraco, A; Herrera, E; Cuetos, F

2016-05-01

Parkinson disease is a neurodegenerative condition involving motor, cognitive, and linguistic deficits. It is important to know why all these different deficits co-occur in the affected people. This paper aims to clarify whether these comorbid deficits result from the selective impairment of a computational primitive, namely, a context-sensitive computational ability according to Chomsky's Hierarchy (a well-established research tool in comparative neuroscience). A total of 15 medicated subjects with Parkinson disease and 15 controls were selected. They were matched in age and education. A battery of tasks was designed to test 3 different domains (motor capacities, cognition, and language) and 2 different computational abilities (context-free and context-sensitive operations). Significant differences between groups were observed only regarding the linguistic task involving context-sensitive computations (correferences). The observed deficits in our patients with Parkinson disease cannot be explained in terms of the selective impairment of one only unspecific, low-level computational process. At the same time, differences between patients and controls are expected to be greater if the former are not medicated. Moreover, we should pursue in the search of (this kind of) computational primitives than can be selectively impaired in people with Parkinson disease, because they may help to achieve an earlier diagnosis of this condition. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of specialist palliative care on coping with Parkinson's disease: patients and carers.

PubMed

Badger, Nathan J; Frizelle, Dorothy; Adams, Debi; Johnson, Miriam J

2018-06-01

UK guidelines recommend palliative care access for people with Parkinson's disease; however, this remains sporadic, and it is unknown whether specialist palliative care helps patients and carers cope with this distressing condition. This study aimed to explore whether, and how, access to specialist palliative care services affected patients' and carers' coping with Parkinson's disease. Semistructured interviews were conducted, audio-recorded and verbatim transcribed. Data were analysed using interpretative phenomenological analysis. Participants were patients with advanced idiopathic Parkinson's disease (n=3), and carers of people with Parkinson's disease (n=5, however, one diagnosis was reviewed) receiving care from an integrated specialist palliative care and Parkinson's disease service in North East England. Access to specialist palliative care helped participants cope with some aspects of advanced Parkinson's disease. Three superordinate themes were developed:' managing uncertainty', 'impacts on the self' and 'specialist palliative care maintaining a positive outlook'. Specialist palliative care helped patients and carers cope with advanced Parkinson's disease. Specialist palliative care is a complex intervention that acknowledges the complex and holistic nature of Parkinson's disease, enabling health in some domains despite continued presence of pathology. These exploratory findings support the utility of this approach for people living with Parkinson's disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

PubMed

Contrera, Joseph F

2011-02-01

The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values. Copyright © 2010 Elsevier Inc. All rights reserved.

[Parkinson's disease in literature, cinema and television].

PubMed

Collado-Vázquez, Susana; Cano-de-la-Cuerda, Roberto; Carrillo, Jesús M

2014-02-01

INTRODUCTION. Since James Parkinson published what can be considered the first treaty on the disease that bears his name in 1817, the scientific literature on this pathology has not ceased to grow. But the illness has also been represented in literature, the cinema and on television, where the symptoms, treatment and socio-familial context of the disease have often been examined very closely. AIM. To address the cases in which Parkinson's disease appears in literature, cinema and television, as well as to reflect on the image of the condition presented in those contexts. DEVELOPMENT. We reviewed some of the most important works in the literature dealing with Parkinson's disease from any period of history and many of them were found to offer very faithful portrayals of the disease. Likewise, we also reviewed major films and TV series that sometimes offer the general public a close look at the vision and the impact of the disease on patients or their relatives. CONCLUSIONS. Literature, cinema and television have helped provide a realistic view of both Parkinson's disease and the related healthcare professionals, and there are many examples that portray the actual experiences of the patients themselves, while also highlighting the importance of healthcare and socio-familial care.

Rasagiline in the pharmacotherapy of Parkinson's disease--a review.

PubMed

Rascol, Olivier

2005-10-01

Despite the current efficacious symptomatic approaches, the search is on for new therapies for Parkinson's disease that can control the cardinal symptoms of the disease (tremor, rigidity and bradykinesia), control/prevent motor complications induced by long-term levodopa, act on non-motor disease symptoms (dementia, dysautonomia, pain, insomnia, falls) and halt disease progression. Rasagiline is a monoamine oxidase-B inhibitor that has demonstrated efficacy against the cardinal symptoms of Parkinson's disease when used as monotherapy in early Parkinson's disease, and as an adjunct to levodopa in advanced disease stages. It reduces the duration and severity of poor symptom response episodes in fluctuating patients. Preliminary results allow discussion of putative effects of rasagiline on some non-motor signs and disease progression. This article outlines the evidence surrounding the efficacy and safety of rasagiline, and discusses its potential to address some of the currently unmet needs of Parkinson's disease therapy.

Lumbar Spine Surgery in Patients with Parkinson Disease.

PubMed

Schroeder, Joshua E; Hughes, Alexander; Sama, Andrew; Weinstein, Joseph; Kaplan, Leon; Cammisa, Frank P; Girardi, Federico P

2015-10-21

Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was <2 in thirteen patients, 2 in thirty patients, 2.5 in twenty-three patients, and ≥3 in thirty patients. The primary indication for surgery was spinal stenosis in seventy-two patients, spondylolisthesis in seventeen patients, and coronal and/or sagittal deformity in seven patients. There were nineteen early complications, including postoperative infections requiring surgical irrigation and debridement and long-term antibiotics in ten patients. The visual analog scale for back pain improved from 7.4 cm preoperatively to 1.8 cm postoperatively (p < 0.001). The visual analog scale for lower-limb pain improved from 7.7 cm preoperatively to 2.3 cm postoperatively (p < 0.001). The Oswestry Disability Index score dropped from 54.1 points to 17.7 points at the time of the latest follow-up (p < 0.001). The Short Form-12 Physical Component Summary score improved from 26.6 points preoperatively to 30.5 points postoperatively (p < 0.05). Twenty patients required revision surgery. Risks for further surgery included a Parkinson disease severity stage of ≥3 (p < 0.05), a history of diabetes mellitus, treatment for osteoporosis, and a combined anterior and posterior approach. Despite a higher rate of complications than in the general population, the

PGC-1a Therapy for Parkinson Neurodegeneration

DTIC Science & Technology

2015-06-01

for Parkinson Neurodegeneration 5a. CONTRACT NUMBER W81XWH-14-1-0123 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Howard Federoff...AWARD NUMBER: W81XWH-14-1-0123 TITLE: PGC-1a Therapy for Parkinson Neurodegeneration PRINCIPAL INVESTIGATOR: Dr. Howard Federoff...Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.

PubMed

Robak, Laurie A; Jansen, Iris E; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Jankovic, Joseph; Heutink, Peter; Shulman, Joshua M

2017-12-01

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-06-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease.

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed Central

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-01-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease. Images PMID:7608666

Effect and Mechanism of Chinese Herbal Medicine on Parkinson's Disease.

PubMed

Zeng, Bai-Yun

2017-01-01

Parkinson's disease is a progressive neurodegenerative disorder. Although both genetic and environmental factors are implicated in the development of Parkinson's disease, the cause of the disease is still unclear. So far conventional treatments to Parkinson's are symptomatic relief and focused mainly on motor symptoms. Chinese herbal medicine has been used to treat many conditions in China, Korea, Japan, and many Southeast Asian countries for 1000 years. During past a few decades, Chinese herbal medicine has gained wider and increasing acceptance within both public and medical profession due to its effectiveness on many conditions in western countries. In this chapter, mechanisms of action of many Chinese herbal compounds/extracts and Chinese herb formulas on the models of Parkinson's were reviewed. Further, reports of effectiveness of Chinese herb formulas on patients with Parkinson's were summarized. It was shown that both Chinese herbal compounds/extracts and herb formulas have either specific target mechanisms of action or multitargets mechanisms of action, as antioxidant, antiinflammatory, and antiapoptosis agents. Clinical studies showed that Chinese herb formulas as an adjunct improved both motor and nonmotor symptoms, and reduced dose of dopaminergic drugs and occurrence of dyskinesia. The evidence from the studies suggests that Chinese herb medicine has potential, acting as neuroprotective to slow down the progression of Parkinson's, and it is able to simultaneously treat both motor and nonmotor symptoms of Parkinson's. More studies are needed to explore the new compounds/extracts derived from Chinese herbs, in particular, their mechanisms of action. It is hopeful that new drugs developed from Chinese herb compounds/extracts and Chinese herb formulas will lead to better and complimentary therapy to PD. © 2017 Elsevier Inc. All rights reserved.

Restless Genital Syndrome Induced by Milnacipran.

PubMed

Miyake, Keita; Takaki, Manabu; Sakamoto, Shinji; Kawada, Kiyohiro; Inoue, Shinichiro; Yamada, Norihito

Restless genital syndrome (RGS) includes discomfort, pain, numbness, vibration, restlessness, or a burning sensation involving the vagina, perineum, pelvis, penis, and proximal portion of the lower limbs in patients. The RGS has been sometimes reported in Parkinson disease. In patients without Parkinson disease, RGS is also known as persistent genital arousal disorder (PSAS), which includes uncontrollable genital arousal, with or without orgasm or genital engorgement, unrelated to sexual desire. Although withdrawal from selective serotonin reuptake inhibitors antidepressants is reported to induce PSAS, there is no report of RGS or PSAS induced by antidepressants. We obtained the consent for the presentation and have not identified individuals for ethical reasons. We first report a woman patient with depression induced RGS by milnacipran (MLN). We discuss the relationship with restless legs syndrome and the difference from akathisia. It is highly possible MLN affected her RGS because she experienced RGS for the first time after the dose of MLN was increased. A limitation of this report is that we stopped MLN and administered gabapentin enacarbil immediately. We should join MLN to the list of compounds suspected of inducing RGS.

Characterization of a Unique Cell Population Marked by Transgene Expression in the Adult Cochlea of Nestin-CreERT2/tdTomato-Reporter Mice

PubMed Central

Chow, Cynthia L.; Guo, Weixiang; Trivedi, Parul; Zhao, Xinyu; Gubbels, Samuel P.

2015-01-01

Hair cells in the adult mammalian cochlea cannot spontaneously regenerate after damage resulting in the permanency of hearing loss. Stem cells have been found to be present in the cochlea of young rodents; however, there has been little evidence for their existence into adulthood. We used nestin-CreERT2/tdTomato-reporter mice to trace the lineage of putative nestin-expressing cells and their progeny in the cochleae of adult mice. Nestin, an intermediate filament found in neural progenitor cells during early development and adulthood, is regarded as a multi-potent and neural stem cell marker. Other investigators have reported its presence in postnatal and young adult rodents; however, there are discrepancies amongst these reports. Using lineage tracing, we documented a robust population of tdTomato-expressing cells and evaluated these cells at a series of adult time points. Upon activation of the nestin promoter, tdTomato was observed just below and medial to the inner hair cell layer. All cells co-localized with the stem cell and cochlear-supporting-cell marker Sox2 as well as the supporting cell and Schwann cell marker Sox10; however, they did not co-localize with the Schwann cell marker Krox20, spiral ganglion marker NF200, or GFAP-expressing supporting cell marker. The cellular identity of this unique population of tdTomato-expressing cells in the adult cochlea of nestin-CreERT2/tdTomato mice remains unclear however these cells may represent a type of supporting cell on the neural aspect of the inner hair cell layer. PMID:25611038

Toxoplasma gondii exposure and Parkinson's disease: a case–control study

PubMed Central

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-01-01

Objectives To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Design Case–control study. Setting Cases and controls were enrolled in Durango City, Mexico. Participants 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Primary and secondary outcome measures Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Results Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. Conclusions The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

PubMed

de Lau, Lonneke M L; Schipper, C Maarten A; Hofman, Albert; Koudstaal, Peter J; Breteler, Monique M B

2005-08-01

Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. General population. A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

PubMed Central

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

Psychosis in parkinsonism: an unorthodox approach

PubMed Central

Onofrj, Marco; Carrozzino, Danilo; D’Amico, Aurelio; Di Giacomo, Roberta; Delli Pizzi, Stefano; Thomas, Astrid; Onofrj, Valeria; Taylor, John-Paul; Bonanni, Laura

2017-01-01

Psychosis in Parkinson’s disease (PD) is currently considered as the occurrence of hallucinations and delusions. The historical meaning of the term psychosis was, however, broader, encompassing a disorganization of both consciousness and personality, including behavior abnormalities, such as impulsive overactivity and catatonia, in complete definitions by the International Classification of Diseases-10 (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Our review is aimed at reminding that complex psychotic symptoms, including impulsive overactivity and somatoform disorders (the last being a recent controversial entity in PD), were carefully described in postencephalitic parkinsonism (PEP), many decades before dopaminergic treatment era, and are now described in other parkinsonisms than PD. Eminent neuropsychiatrists of the past century speculated that studying psychosis in PEP might highlight its mechanisms in other conditions. Yet, functional assessments were unavailable at the time. Therefore, the second part of our article reviews the studies of neural correlates of psychosis in parkinsonisms, by taking into account both theories on the narrative functions of the default mode network (DMN) and hypotheses on DMN modulation. PMID:28553118

Complete Genome Sequences of Lactobacillus johnsonii Strain N6.2 and Lactobacillus reuteri Strain TD1.

PubMed

Leonard, Michael T; Valladares, Ricardo B; Ardissone, Alexandria; Gonzalez, Claudio F; Lorca, Graciela L; Triplett, Eric W

2014-05-08

We report here the complete genome sequences of Lactobacillus johnsonii strain N6.2, a homofermentative lactic acid intestinal bacterium, and Lactobacillus reuteri strain TD1, a heterofermentative lactic acid intestinal bacterium, both isolated from a type 1 diabetes-resistant rat model.

Aged monkeys as a partial model for Parkinson's disease.

PubMed

Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E

2011-09-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. Copyright © 2011 Elsevier Inc

Data protection in biomaterial banks for Parkinson's disease research: the model of GEPARD (Gene Bank Parkinson's Disease Germany).

PubMed

Eggert, Karla; Wüllner, Ullrich; Antony, Gisela; Gasser, Thomas; Janetzky, Bernd; Klein, Christine; Schöls, Ludger; Oertel, Wolfgang

2007-04-15

Parkinson's disease (PD) is the second most common neurodegenerative disease. Although 10 gene loci have been identified to cause a Parkinsonian syndrome, these loci account only for a minority of PD patients. Large, systematic research programs are required to collect, store, and analyze DNA samples and clinical information to support further discovery of additional genetic components of PD or other movement disorders. Such programs facilitate research into the relationship between genotype and phenotype. The German Competence Network on Parkinson's disease (CNP) initiated the Gene Bank Parkinson's Disease Germany (GEPARD), providing an administrative and scientific infrastructure for the storage of DNA and clinical data that are electronically accessible and protective of patient rights. In this article, we offer guidance on how to establish a framework for a clinical genetic data and DNA bank, and describe GEPARD as a model that may be useful to other local, national, and international research groups developing similar programs.

Restless legs syndrome: an early clinical feature of Parkinson disease in men.

PubMed

Wong, Janice C; Li, Yanping; Schwarzschild, Michael A; Ascherio, Alberto; Gao, Xiang

2014-02-01

The association between restless legs syndrome (RLS) and Parkinson disease has been extensively studied, but the temporal relationship between the two remains unclear. We thus conduct the first prospective study to examine the risk of developing Parkinson disease in RLS. Prospective study from 2002-2010. United States. There were 22,999 US male health professionals age 40-75 y enrolled in the Health Professionals Follow-up Study without Parkinson disease, arthritis, or diabetes mellitus at baseline. RLS was assessed in 2002 using a set of standardized questions recommended by the International RLS Study Group. Incident Parkinson disease was identified by biennial questionnaires and then confirmed by review of participants' medical records by a movement disorder specialist. We documented 200 incident Parkinson disease cases during 8 y of follow-up. Compared to men without RLS, men with RLS symptoms who had symptoms greater than 15 times/mo had higher risk of Parkinson disease development (adjusted relative risk = 1.47; 95% confidence interval: 0.59, 3.65; P = 0.41). This was statistically significant only for cases diagnosed within 4 y of follow-up (adjusted relative risk = 2.77; 95% confidence interval: 1.08, 7.11; P = 0.03). Severe restless legs syndrome may be an early feature of Parkinson disease.

Hot corrosion of four superalloys - HA-188, S-57, IN-617, and TD-NiCrAl

NASA Technical Reports Server (NTRS)

Santoro, G. J.

1979-01-01

Cyclic oxidation and hot corrosion tests of two cobalt-base and two nickel-base alloys are reported. The alloys were exposed to maximum temperatures of 900 and 1000 C in a Mach 0.3 burner rig whose flame was doped with various concentrations of sea salt and sodium sulfate for hot corrosion tests. The test data were subjected to a regression analysis for the development of model equations relating corrosion to temperature and for the effects of salt concentration and composition on corrosion. The corrosion resistance varied with temperature, sea salt concentration, and salt composition, concluding that the S-57 cobalt-base alloy was the most hot corrosion-resistant alloy, and the TD-NiCrAl nickel-base alloy was the least resistant. However, under straight oxidation conditions, the TD-NiCrAl was most resistant, while S-57 was the least resistant alloy.

Extensive TD-DFT Benchmark: Singlet-Excited States of Organic Molecules.

PubMed

Jacquemin, Denis; Wathelet, Valérie; Perpète, Eric A; Adamo, Carlo

2009-09-08

Extensive Time-Dependent Density Functional Theory (TD-DFT) calculations have been carried out in order to obtain a statistically meaningful analysis of the merits of a large number of functionals. To reach this goal, a very extended set of molecules (∼500 compounds, >700 excited states) covering a broad range of (bio)organic molecules and dyes have been investigated. Likewise, 29 functionals including LDA, GGA, meta-GGA, global hybrids, and long-range-corrected hybrids have been considered. Comparisons with both theoretical references and experimental measurements have been carried out. On average, the functionals providing the best match with reference data are, one the one hand, global hybrids containing between 22% and 25% of exact exchange (X3LYP, B98, PBE0, and mPW1PW91) and, on the other hand, a long-range-corrected hybrid with a less-rapidly increasing HF ratio, namely LC-ωPBE(20). Pure functionals tend to be less consistent, whereas functionals incorporating a larger fraction of exact exchange tend to underestimate significantly the transition energies. For most treated cases, the M05 and CAM-B3LYP schemes deliver fairly small deviations but do not outperform standard hybrids such as X3LYP or PBE0, at least within the vertical approximation. With the optimal functionals, one obtains mean absolute deviations smaller than 0.25 eV, though the errors significantly depend on the subset of molecules or states considered. As an illustration, PBE0 and LC-ωPBE(20) provide a mean absolute error of only 0.14 eV for the 228 states related to neutral organic dyes but are completely off target for cyanine-like derivatives. On the basis of comparisons with theoretical estimates, it also turned out that CC2 and TD-DFT errors are of the same order of magnitude, once the above-mentioned hybrids are selected.

Parkinsonism is associated to fronto-caudate disconnectivity and cognition in schizophrenia.

PubMed

Molina, Vicente; Lubeiro, Alba; Blanco, Jorge; Blanco, José A; Rodríguez, Margarita; Rodríguez-Campos, Alicia; de Luis-García, Rodrigo

2018-07-30

The present work studies the possible relation of parkinsonism and fronto-caudate dysconnectivity, as well as its relation to cognition in schizophrenia patients. We assessed parkinsonism using Simpson-Angus scale and prefronto-caudate connectivity using diffusion magnetic resonance in 22 schizophrenia patients (11 first-episodes) and 14 healthy controls. Fractional anisotropy was calculated for the white matter tracts directly linking rostral middle prefrontal (RMPF) and superior medial prefrontal (SMPF) regions with caudate nucleus. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia Scale (BACS). Total parkinsonism scores were negatively related to fractional anisotropy in the right SMPF-caudate tract in patients, which was also found in the first-episode patients alone, but not in controls. Parkinsonism was also inversely associated in patients to performance in social cognition, verbal memory, working memory and performance speed tests. In conclusion, our data support the involvement of fronto-striatal dysconnectivity in parkinsonism in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Exercise Training and Parkinson's Disease: Placebo or Essential Treatment?

ERIC Educational Resources Information Center

Reuter, Iris; Engelhardt, Martin

2002-01-01

Exercise training is often recommended for people with Parkinson's disease, though there is debate about the pathophysiologic cause of impaired movement in Parkinsonism which makes it difficult to develop a specific exercise treatment for symptoms that include hypokinesia, tremor, and muscular rigidity. Most published studies show a benefit of…

Clear Speech Variants: An Acoustic Study in Parkinson's Disease

ERIC Educational Resources Information Center

Lam, Jennifer; Tjaden, Kris

2016-01-01

Purpose: The authors investigated how different variants of clear speech affect segmental and suprasegmental acoustic measures of speech in speakers with Parkinson's disease and a healthy control group. Method: A total of 14 participants with Parkinson's disease and 14 control participants served as speakers. Each speaker produced 18 different…

Herpes zoster correlates with increased risk of Parkinson's disease in older people

PubMed Central

Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

2017-01-01

Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

The intrinsic resting state voice network in Parkinson's disease

PubMed Central

New, Anneliese B.; Parkinson, Amy L.; Eickhoff, Claudia R.; Reetz, Kathrin; Hoffstaedter, Felix; Mathys, Christian; Sudmeyer, Martin; Michely, Jochen; Caspers, Julian; Grefkes, Christian; Larson, Charles R.; Ramig, Loraine O.; Fox, Peter T.; Eickhoff, Simon B.

2015-01-01

Abstract Over 90 percent of patients with Parkinson's disease experience speech‐motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting‐state functional connectivity analysis of blood oxygen level‐dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting‐state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta‐analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender‐, age‐, and movement‐matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ‐39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within‐group analyses of connectivity patterns demonstrated a lack of subcortical–cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease. Hum Brain Mapp 36:1951–1962, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627959

Counterfactual cognitive deficit in persons with Parkinson's disease

PubMed Central

McNamara, P; Durso, R; Brown, A; Lynch, A

2003-01-01

Background: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making—all processes independently linked to the frontal lobes. Objective: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson's disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson's disease and 15 age matched healthy controls. Results. Patients with Parkinson's disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour–word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. Conclusions: Counterfactual thinking is impaired in Parkinson's disease. This impairment may be related to frontal lobe dysfunction. PMID:12876235

Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

PubMed Central

Marrakchi, S.; Kammoun, I.; Kachboura, S.

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope. PMID:25114686

Wolff-Parkinson-white syndrome mimics a conduction disease.

PubMed

Marrakchi, S; Kammoun, I; Kachboura, S

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

Tension-referenced measures of gastrocnemius slack length and stiffness in Parkinson's disease.

PubMed

Tan, Benedict; Double, Kay L; Burne, John; Diong, Joanna

2016-12-01

It is not known how passive muscle length and stiffness contribute to rigidity in Parkinson's disease. The objective of this study was to compare passive gastrocnemius muscle-tendon slack length and stiffness at known tension in Parkinson's disease subjects with ankle rigidity and in able-bodied people. Passive ankle torque-angle curves were obtained from 15 Parkinson's disease subjects with rigidity and 15 control subjects. Torque-angle data were used to derive passive gastrocnemius length-tension data and calculate slack length and stiffness of the gastrocnemius muscle. Between-group comparisons were made with linear models. Gastrocnemius muscle-tendon slack lengths (adjusted between-group difference, 0.01 m; 95% CI, -0.02 to 0.04 m; P = 0.37) and stiffness (adjusted between-group difference, 15.7 m -1 ; 95% CI, -8.5 to 39.9 m -1 ; P = 0.19) were not significantly different between groups. Parkinson's disease subjects with ankle rigidity did not have significantly shorter or stiffer gastrocnemius muscles compared with control subjects. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Learning about Parkinson's Disease

MedlinePlus

... having genetic testing can learn more about their risk for Parkinson's disease and the availability and accuracy of genetic testing for this disease by setting up an appointment with a genetics health professional. Genetic professionals work as members of health ...

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

PubMed

Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

2017-08-01

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year

[Morphochemical changes in the substantia nigra cellular structures in Parkinson's disease].

PubMed

Salkov, V N; Khudoerkov, R M; Voronkov, D N; Sobolev, V B; Kutukova, K A

to clarify the features of morphochemical changes in the substantia nigra cellular structures in Parkinson's disease. The structural characteristics of the substantia nigra were studied microscopically and quantified using computer morphometric methods at brain autopsies of individuals with Parkinson's disease who had died from intercurrent diseases and those who had no evidence of neurological disorders in their history (a control group). This investigation could clarify the features of morphochemical changes in both the neural network structures and the glial populations of the substantia nigra in Parkinson's disease. The number of neurons containing tyrosine hydroxylase (a marker of dopamine neurons) in the compact part of the substantia nigra (a ventral region) was smaller and the density distribution of Lewy bodies was higher in the patients with Parkinson's disease than in the control group. The accumulation of iron (II) compounds in the cellular elements and neuropile and the increased expression of glial fibrillary acidic protein in Parkinson's disease were more pronounced than those in the controls. Postmortem diagnosis in Parkinson's disease should be based on a full description of a set of neuronal and glial morphochemical and structural changes in the substantia nigra rather than on the identification of cellular markers for the neurodegenerative process.

Molecular chaperones in Parkinson's disease--present and future.

PubMed

Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

2011-01-01

Parkinson's disease, like many other neurodegenerative disorders, is characterized by the progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. The cascade by which the small synaptic protein α-synuclein misfolds to form distinctive protein aggregates, termed Lewy bodies and Lewy neurites, has been the subject of intensive research for more than a decade. Genetic and pathological studies in Parkinson's disease patients as well as experimental studies in disease models have clearly established altered protein metabolism as a key element in the pathogenesis of Parkinson's disease. Alterations in protein metabolism include misfolding and aggregation, post-translational modification and dysfunctional degradation of cytotoxic protein species. Protein folding and re-folding are both mediated by a highly conserved network of molecules, called molecular chaperones and co-chaperones. In addition to the regulatory role in protein folding, molecular chaperone function is intimately associated with pathways of protein degradation, such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway, to effectively remove irreversibly misfolded proteins. Because of the central role of molecular chaperones in maintaining protein homeostasis, we herein review our current knowledge on the involvement of molecular chaperones and co-chaperones in Parkinson's disease. We further discuss the capacity of molecular chaperones to prevent or modulate neurodegeneration, an important concept for future neuroprotective strategies and summarize the current progress in preclinical studies in models of Parkinson's disease and other neurodegenerative disorders. Finally we include a discussion on the future potential of using molecular chaperones as a disease modifying therapy.

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

PubMed Central

Martinez, Terina N.

2012-01-01

Abstract Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920–934. PMID:21554057

Effects of exercise on mobility in people with Parkinson's disease.

PubMed

van der Kolk, Nicolien M; King, Laurie A

2013-09-15

Parkinson's disease is a prevalent neurodegenerative disorder for which only symptomatic treatment exists. Gait and balance disturbance is common in Parkinson's disease and is a major contributor to increased disability and decreased health-related quality of life and survival. Balance and gait deficits in Parkinson's disease are notoriously difficult to treat and are not significantly helped by pharmacological or surgical treatment. The last two decades have seen a dramatic increase in the research and clinical interest in using exercise as a treatment for mobility problems in people with Parkinson's disease. With exciting advances in basic science research suggesting neurochemical and neuroplastic changes after exercise, an increasing number of high-quality studies are documenting particular aspects of mobility improving after exercise. Exercise has the potential to help both motor (gait, balance, strength) and nonmotor (depression, apathy, fatigue, constipation) aspects of Parkinson's disease as well as secondary complications of immobility (cardiovascular, osteoporosis). This perspective article focuses primarily on recent evidence on the effects of exercise in improving mobility while highlighting the importance of targeted exercise intervention for maximizing the benefits of exercise. Suggestions for exercise guidelines, adherence issues, and directions for future research are provided. © 2013 Movement Disorder Society.

How Is Parkinson's Disease Treated?

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

PubMed

Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

2015-01-01

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

[Juvenile Parkinson's disease and recurring prematurity. Case report].

PubMed

Ha, D-E; Legendre, G; Colau, J-C

2007-03-01

The association of Parkinson's disease and pregnancy is very rare. Some thirty cases are found in the literature. We report the case of a pregnancy in a 30-year-old patient with juvenile Parkinson's disease. During this pregnancy treated by levodopa and bromocriptine, no aggravation of the symptoms was been observed. However, the pregnancy was complicated by a premature delivery at 31 weeks of amenorrhoea.

Michael J. Fox and his Parkinson's disease.

PubMed

Kempster, Peter A

2004-01-01

Michael J. Fox was a popular and successful film and television comic actor who developed Parkinson's disease at the age of 29 years. His recently published book, Lucky Man, structured around the story of his Parkinson's disease, is an amusing, briskly paced yet introspective memoir that covers the first 40 years of his life. Although quite anecdotal, it contains interesting observations on the preclinical phase of the disorder, evolution of motor fluctuations, and tactics for pharmacological treatment. Copyright 2003 Movement Disorder Society

Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

PubMed

Haapaniemi, T H; Pursiainen, V; Korpelainen, J T; Huikuri, H V; Sotaniemi, K A; Myllylä, V V

2001-03-01

Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

Primary Health Care Providers' Knowledge Gaps on Parkinson's Disease

ERIC Educational Resources Information Center

Thompson, Megan R.; Stone, Ramona F.; Ochs, V. Dan; Litvan, Irene

2013-01-01

In order to determine primary health care providers' (PCPs) knowledge gaps on Parkinson's disease, data were collected before and after a one-hour continuing medical education (CME) lecture on early Parkinson's disease recognition and treatment from a sample of 104 PCPs participating at an annual meeting. The main outcome measure was the…

Early Pleistocene hominin deciduous teeth from the Homo antecessor Gran Dolina-TD6 bearing level (Sierra de Atapuerca, Spain).

PubMed

Bermúdez de Castro, José María; Martinón-Torres, María; Martín-Francés, Laura; Martínez de Pinillos, Marina; Modesto-Mata, Mario; García-Campos, Cecilia; Wu, Xiujie; Xing, Song; Liu, Wu

2017-07-01

During the last 13 years, the late Early Pleistocene Gran Dolina-TD6-2 level (Sierra de Atapuerca, northern Spain) has yielded an additional sample of 26 dental specimens attributed to Homo antecessor. In this report, we present a descriptive and comparative study of the six deciduous teeth. We provide external and internal morphological descriptions following classical terminology, as well as the mesiodistal and buccolingual measurements of the teeth. The internal morphology was described by means of micro-CT technique. The TD6 deciduous teeth preserve primitive features regarding the Homo clade, such as the presence of styles in lower and upper canines and developed anterior and posterior foveae in the dm 2 . However, other features related to the complexity of the crown morphology (e.g., cingulum) are not present in this sample. Furthermore, the great reduction of the talonid of the dm 1 s is also noteworthy. Despite the limited comparative evidence, the presence of a remarkably well-developed tuberculum molare in the dm 1 and dm 1 s from TD6 can be also considered a derived feature in the genus Homo. The TD6 hominins exhibit dental dimensions similar to those of other Pleistocene hominins. The dm 1 s are buccolingually elongated and the buccolingual diameter of ATD6-93 is the largest recorded so far in the Homo fossil record. This study expands the list of plesiomorphic features of H. antecessor, and provides some information on the evolutionary status of this species. However, the identification of some advanced traits evinces a step towards the derived morphology of European Pleistocene teeth. The study of the deciduous dentition confirms the mosaic pattern of H. antecessor morphology revealed in previous studies of this hominin sample. © 2017 Wiley Periodicals, Inc.

Risk of Falls in Parkinson's Disease: A Cross-Sectional Study of 160 Patients

PubMed Central

Contreras, Ana; Grandas, Francisco

2012-01-01

Falls are a major source of disability in Parkinson's disease. Risk factors for falling in Parkinson's disease remain unclear. To determine the relevant risk factors for falling in Parkinson's disease, we screened 160 consecutive patients with Parkinson's disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson's disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson's disease experienced falls significantly earlier than younger patients. PMID:22292126

Treadmill exercise alleviates nigrostriatal dopaminergic loss of neurons and fibers in rotenone-induced Parkinson rats.

PubMed

Shin, Mal-Soon; Kim, Tae-Woon; Lee, Jae-Min; Ji, Eun-Sang; Lim, Baek-Vin

2017-02-01

Parkinson disease is one of the common brain diseases caused by dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. In the present study, the effects of treadmill exercise on motor performance, dopaminergic loss of neurons and fibers, and α-synuclein expression in the nigrostriatum were evaluated using rotenone-induced Parkinson rats. For the induction of Parkinson rats, 3-mg/kg rotenone was injected, once a day for 14 consecutive days. Treadmill running was conducted for 30 min once a day during 14 consecutive days. Rota-rod test for motor balance and coordination and immunohistochemistry for tyrosine hydroxylase and α-synuclein in the nigrostriatum were performed. In the present study, motor balance and coordination was disturbed by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated motor dysfunction in the rotenone-induced Parkinson rats. Nigrostriatal dopaminergic loss of neurons and fibers was occurred by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise alleviated nigrostriatal dopaminergic loss of neurons and fibers in the rotenone-induced Parkinson rats. α-Synuclein expression in the nigrostriatum was enhanced by induction of rotenone-induced Parkinson disease, in contrast, treadmill exercise suppressed α-synuclein expression in the rotenone-induced Parkinson rats. Treadmill exercise improved motor function through preservation of nigrostriatal dopaminergic neurons and fibers and suppression of nigrostriatal formation of Lewy bodies in rotenone-induced Parkinson rats.

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-02-13

To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Case-control study. Cases and controls were enrolled in Durango City, Mexico. 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Serum samples of participants were analysed for anti- T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Anti- T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti- T. gondii IgG positive cases and four of the anti- T. gondii IgG positive controls had anti- T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not

Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus.

PubMed

Dirkx, Michiel F; den Ouden, Hanneke E M; Aarts, Esther; Timmer, Monique H M; Bloem, Bastiaan R; Toni, Ivan; Helmich, Rick C

2017-03-01

Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role

Quantitative Motor Performance and Sleep Benefit in Parkinson Disease

PubMed Central

van Gilst, Merel M.; van Mierlo, Petra; Bloem, Bastiaan R.; Overeem, Sebastiaan

2015-01-01

Study Objectives: Many people with Parkinson disease experience “sleep benefit”: temporarily improved mobility upon awakening. Here we used quantitative motor tasks to assess the influence of sleep on motor functioning in Parkinson disease. Design: Eighteen Parkinson patients with and 20 without subjective sleep benefit and 20 healthy controls participated. Before and directly after a regular night sleep and an afternoon nap, subjects performed the timed pegboard dexterity task and quantified finger tapping task. Subjective ratings of motor functioning and mood/vigilange were included. Sleep was monitored using polysomnography. Results: On both tasks, patients were overall slower than healthy controls (night: F2,55 = 16.938, P < 0.001; nap: F2,55 = 15.331, P < 0.001). On the pegboard task, there was a small overall effect of night sleep (F1,55 = 9.695, P = 0.003); both patients and controls were on average slightly slower in the morning. However, in both tasks there was no sleep*group interaction for nighttime sleep nor for afternoon nap. There was a modest correlation between the score on the pegboard task and self-rated motor symptoms among patients (rho = 0.233, P = 0.004). No correlations in task performance and mood/vigilance or sleep time/efficiency were found. Conclusions: A positive effect of sleep on motor function is commonly reported by Parkinson patients. Here we show that the subjective experience of sleep benefit is not paralleled by an actual improvement in motor functioning. Sleep benefit therefore appears to be a subjective phenomenon and not a Parkinson-specific reduction in symptoms. Citation: van Gilst MM, van Mierlo P, Bloem BR, Overeem S. Quantitative Motor Performance and Sleep Benefit in Parkinson Disease. SLEEP 2015;38(10):1567–1573. PMID:25902811

State-of-technology for joining TD-NiCr sheet

NASA Technical Reports Server (NTRS)

Holko, K. H.; Moore, T. J.; Gyorgak, C. A.

1972-01-01

At the current state-of-technology there are many joining processes that can be used to make sound welds in TD-NiCr sheet. Some of these that are described in this report are electron beam welding, gas-tungsten arc welding, diffusion welding, resistance spot welding, resistance seam welding, and brazing. The strengths of the welds made by the various processes show considerable variation, especially at elevated temperatures. Most of the fusion welding processes tend to give weak welds at elevated temperatures (with the exception of fusion-type resistance spotwelds). However, solid-state welds have been made with parent metal properties. The process used for a specific application will be dictated by the specific joint requirements. In highly stressed joints at elevated temperatures, one of the solid-state processes, such as DFW, RSW (solid-state or fusion), and RSEW, offer the most promise.

[Nature of speech disorders in Parkinson disease].

PubMed

Pawlukowska, W; Honczarenko, K; Gołąb-Janowska, M

2013-01-01

The aim of the study was to discuss physiology and pathology of speech and review of the literature on speech disorders in Parkinson disease. Additionally, the most effective methods to diagnose the speech disorders in Parkinson disease were also stressed. Afterward, articulatory, respiratory, acoustic and pragmatic factors contributing to the exacerbation of the speech disorders were discussed. Furthermore, the study dealt with the most important types of speech treatment techniques available (pharmacological and behavioral) and a significance of Lee Silverman Voice Treatment was highlighted.

Palliative care for Parkinson's disease: Patient and carer's perspectives explored through qualitative interview.

PubMed

Fox, Siobhan; Cashell, Alison; Kernohan, W George; Lynch, Marie; McGlade, Ciara; O'Brien, Tony; O'Sullivan, Sean S; Foley, Mary J; Timmons, Suzanne

2017-07-01

Palliative care is recommended for non-malignant illnesses, including Parkinson's disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a 'fear' in their patients about introducing palliative care. However, less is known about the views of people with Parkinson's disease and their carers about palliative care. (1) To explore the palliative care and related issues most affecting people with Parkinson's disease and their families and (2) to examine perceptions about/understanding of palliative care. This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis. A total of 31 people participated, both people with Parkinson's disease ( n = 19) and carers ( n = 12), across three Movement Disorder Clinics in the Republic of Ireland. People with Parkinson's disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson's disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs. A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson's disease and their carers, and people with Parkinson's disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson's disease.

Seasonal temperature is associated with Parkinson's disease prescriptions: an ecological study

NASA Astrophysics Data System (ADS)

Rowell, David; Nghiem, Son; Ramagopalan, Sreeram; Meier, Ute-Christiane

2017-12-01

The aim of this study is to test what effect the weather may have on medications prescribed to treat Parkinson's disease. Twenty-three years of monthly time, series data was sourced from the Pharmaceutical Benefits Scheme (PBS) and the Bureau of Meteorology (BOM). Data were available for eight states and territories and their corresponding capital cities. The dependent variable was the aggregate levodopa equivalent dose (LED) for 51 Parkinson's medications identified on the PBS. Two explanatory variables of interest, temperature and solar exposure, were identified in the BOM data set. Linear and cosinor models were estimated with fixed and random effects, respectively. The prescribed LED was 4.2% greater in January and 4.5% lower in July. Statistical analysis showed that temperature was associated with the prescription of Parkinson medications. Our results suggest seasonality exists in Parkinson's disease symptoms and this may be related to temperature. Further work is needed to confirm these findings and understand the underlying mechanisms as a better understanding of the causes of any seasonal variation in Parkinson's disease may help clinicians and patients manage the disease more effectively.

A mixed-methods study into ballet for people living with Parkinson's.

PubMed

Houston, Sara; McGill, Ashley

2013-06-01

Background : Parkinson's is a neurological disease that is physically debilitating and can be socially isolating. Dance is growing in popularity for people with Parkinson's and claims have been made for its benefits. The paper details a mixed-methods study that examined a 12-week dance project for people with Parkinson's, led by English National Ballet. Methods : The effects on balance, stability and posture were measured through the Fullerton Advanced Balance Scale and a plumb-line analysis. The value of participation and movement quality were interpreted through ethnographic methods, grounded theory and Effort analysis. Results : Triangulation of results indicates that people were highly motivated, with 100% adherence, and valued the classes as an important part of their lives. Additionally, results indicated an improvement in balance and stability, although not in posture. Conclusions : Dancing may offer benefit to people with Parkinson's through its intellectual, artistic, social and physical aspects. The paper suggests that a range of research methods is fundamental to capture the importance of multifaceted activity, such as dance, to those with Parkinson's.

Rasch analysis of the carers quality of life questionnaire for parkinsonism.

PubMed

Pillas, Marios; Selai, Caroline; Schrag, Anette

2017-03-01

To assess the psychometric properties of the Carers Quality of Life Questionnaire for Parkinsonism using a Rasch modeling approach and determine the optimal cut-off score. We performed a Rasch analysis of the survey answers of 430 carers of patients with atypical parkinsonism. All of the scale items demonstrated acceptable goodness of fit to the Rasch model. The scale was unidimensional and no notable differential item functioning was detected in the items regarding age and disease type. Rating categories were functioning adequately in all scale items. The scale had high reliability (.95) and construct validity and a high degree of precision, distinguishing between 5 distinct groups of carers with different levels of quality of life. A cut-off score of 62 was found to have the optimal screening accuracy based on Hospital Anxiety and Depression Scale subscores. The results suggest that the Carers Quality of Life Questionnaire for Parkinsonism is a useful scale to assess carers' quality of life and allows analyses requiring interval scaling of variables. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

PubMed

Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

2018-05-01

Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.

PubMed

Segura-Aguilar, Juan

2017-06-01

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson's disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson's disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson's disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

Familial Hemiplegic Migraine Type 1 Associated with Parkinsonism: A Case Report

PubMed Central

Bruun, Marie; Hjermind, Lena Elisabeth; Thomsen, Carsten; Danielsen, Else; Thomsen, Lise Lykke; Pinborg, Lars Hageman; Khabbazbavani, Nastaran; Nielsen, Joergen Erik

2015-01-01

Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present with cerebellar signs, but parkinsonism has not previously been reported in FHM1 or EA2 even though parkinsonism has been described in SCA6. We report a 63-year-old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically presenting with migraine and permanent cerebellar ataxia. Since the age of 60 years, the patient also developed parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission computed tomography demonstrated a decreased DAT-binding potential in the putamen. We wish to draw attention to FHM1 associated with parkinsonism; however, whether the reported case is a consequence of FHM1 being allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or idiopathic Parkinson's disease remains unanswered. PMID:25969684

Parkinson's disease: the spectrum of disabilities.

PubMed Central

Pentland, B; Barnes, M P; Findley, L J; Oxtoby, M; Pearce, V R; Quinn, N P; Scott, S

1992-01-01

The needs of people with Parkinson's disease (PD) go beyond the purely medical domain and often require collaborative management. A Panel Discussion at the "Hither neurology" Symposium included neurologists, a speech therapist, a geriatrician and a sociologist. Their discussion highlighted certain aspects of the disability and disadvantage associated with PD. The starting point was a video recording, "Parkinson's Disease: the personal view", in which the contributors were patients and carers. Topics covered included counselling at the time of diagnosis; subsequent access to clinics and to neurological advice; access to therapy; support in the community; fluctuating disability associated with "on-off" phenomena; driving; and sexual problems. PMID:1564503

Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

ClinicalTrials.gov

2018-02-27

Idiopathic Parkinson's Disease; Parkinson's Disease; Basal Ganglia Disease; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

Prying into the Prion Hypothesis for Parkinson's Disease.

PubMed

Brundin, Patrik; Melki, Ronald

2017-10-11

In Parkinson's disease, intracellular α-synuclein inclusions form in neurons. We suggest that prion-like behavior of α-synuclein is a key component in Parkinson's disease pathogenesis. Although multiple molecular changes are involved in the triggering of the disease process, we propose that neuron-to-neuron transfer is a crucial event that is essential for Lewy pathology to spread from one brain region to another. In this review, we describe key findings in human postmortem brains, cultured cells, and animal models of disease that support the idea that α-synuclein can act as a prion. We consider potential triggers of the α-synuclein misfolding and why the aggregates escape cellular degradation under disease conditions. We also discuss whether different strains of α-synuclein fibrils can underlie differences in cellular and regional distribution of aggregates in different synucleinopathies. Our conclusion is that α-synuclein probably acts as a prion in human diseases, and a deeper understanding of this step in the pathogenesis of Parkinson's disease can facilitate the development of disease-modifying therapies in the future. Dual Perspectives Companion Paper: Parkinson's Disease Is Not Simply a Prion Disorder, by D. James Surmeier, José A. Obeso, and Glenda M. Halliday. Copyright © 2017 the authors 0270-6474/17/379808-11$15.00/0.

Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.

PubMed

Wahabi, Khushnuma; Perwez, Ahmad; Rizvi, Moshahid A

2018-01-18

Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers. It is hard to imagine that two entirely different classes of disease, like cancer and Parkinson's disease, can converge at a critical point attributable to a single gene, Parkin. This mysterious and hidden connection may prove a boon in disguise and has raised hopes that studying the biology of one disease may help to identify novel targets of therapy for the other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway is unraveled and gaps in the storyline are properly filled up, we may end getting an entirely new therapeutic option. This review mainly highlights the recent literature which suggests how Parkin gene regulates the various hallmarks of both the Parkinson's disease and cancer.

Control effects of stimulus paradigms on characteristic firings of parkinsonism

NASA Astrophysics Data System (ADS)

Zhang, Honghui; Wang, Qingyun; Chen, Guanrong

2014-09-01

Experimental studies have shown that neuron population located in the basal ganglia of parkinsonian primates can exhibit characteristic firings with certain firing rates differing from normal brain activities. Motivated by recent experimental findings, we investigate the effects of various stimulation paradigms on the firing rates of parkinsonism based on the proposed dynamical models. Our results show that the closed-loop deep brain stimulation is superior in ameliorating the firing behaviors of the parkinsonism, and other control strategies have similar effects according to the observation of electrophysiological experiments. In addition, in conformity to physiological experiments, we found that there exists optimal delay of input in the closed-loop GPtrain|M1 paradigm, where more normal behaviors can be obtained. More interestingly, we observed that W-shaped curves of the firing rates always appear as stimulus delay varies. We furthermore verify the robustness of the obtained results by studying three pallidal discharge rates of the parkinsonism based on the conductance-based model, as well as the integrate-and-fire-or-burst model. Finally, we show that short-term plasticity can improve the firing rates and optimize the control effects on parkinsonism. Our conclusions may give more theoretical insight into Parkinson's disease studies.

Using single top rapidity to measure V{sub td}, V{sub ts}, V{sub tb} at hadron colliders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguilar-Saavedra, J. A.; Onofre, A.; Departamento de Fisica, Universidade do Minho, P-4710-057 Braga

2011-04-01

Single top production processes are usually regarded as the ones in which V{sub tb} can be directly measured at hadron colliders. We show that the analysis of the single top rapidity distribution in t-channel and tW production can also set direct limits on V{sub td}. At LHC with 10 fb{sup -1} at 14 TeV, the combined limits on V{sub td} may be reduced by almost a factor of 2 when the top rapidity distribution is used. This also implies that the limits on V{sub tb} can also be reduced by 15%, since both parameters, as well as V{sub ts}, mustmore » be simultaneously obtained from a global fit to data. At Tevatron, the exploitation of this distribution would require very high statistics.« less

[Emotional facial expression recognition impairment in Parkinson disease].

PubMed

Lachenal-Chevallet, Karine; Bediou, Benoit; Bouvard, Martine; Thobois, Stéphane; Broussolle, Emmanuel; Vighetto, Alain; Krolak-Salmon, Pierre

2006-03-01

some behavioral disturbances observed in Parkinson's disease (PD) could be related to impaired recognition of various social messages particularly emotional facial expressions. facial expression recognition was assessed using morphed faces (five emotions: happiness, fear, anger, disgust, neutral), and compared to gender recognition and general cognitive assessment in 12 patients with Parkinson's disease and 14 controls subjects. facial expression recognition was impaired among patients, whereas gender recognitions, visuo-perceptive capacities and total efficiency were preserved. Post hoc analyses disclosed a deficit for fear and disgust recognition compared to control subjects. the impairment of emotional facial expression recognition in PD appears independent of other cognitive deficits. This impairment may be related to the dopaminergic depletion in basal ganglia and limbic brain regions. They could take a part in psycho-behavioral disorders and particularly in communication disorders observed in Parkinson's disease patients.

Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study.

PubMed

Biundo, Roberta; Weis, Luca; Abbruzzese, Giovanni; Calandra-Buonaura, Giovanna; Cortelli, Pietro; Jori, Maria Cristina; Lopiano, Leonardo; Marconi, Roberto; Matinella, Angela; Morgante, Francesca; Nicoletti, Alessandra; Tamburini, Tiziano; Tinazzi, Michele; Zappia, Mario; Vorovenci, Ruxandra Julia; Antonini, Angelo

2017-11-01

Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia. The ALTHEA study enrolled 251 Parkinson's disease patients with various degrees of dyskinesia severity from 11 movement disorders centers in Italy. Each patient underwent a comprehensive assessment including Unified Dyskinesia Rating Scale and the Questionnaire for Impulsive Compulsive Disorders in Parkinson Disease-Rating Scale. There was an overall 55% frequency of impulse control disorder and related behaviors (36% were clinically significant). The positive patients were younger at disease diagnosis and onset and had higher Unified Dyskinesia Rating Scale historical and total score (P = 0.001 and P = 0.02, respectively, vs negative). There was an increased frequency of clinically significant impulse control disorders in patients with severe dyskinesia (P = 0.013), a positive correlation between the questionnaire total score and dopamine agonist dose (P = 0.018), and a trend with levodopa dose. More than half of Parkinson's disease patients with dyskinesia have impulse control disorders and related behaviors, which are frequently clinically significant. Dopaminergic therapy total dose is associated with their severity. Clinicians should carefully assess patients with maladaptive behaviors and dyskinesia because they do not properly evaluate their motor and nonmotor status. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Greater risk of parkinsonism associated with non-N370S GBA1 mutations

PubMed Central

Giraldo, P.; Capablo, J. L.; Alfonso, P.; Irun, P.; Garcia-Rodriguez, B.; Pocovi, M.; Pastores, G. M.

2014-01-01

Mutations in β-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkin-sonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR=22.5; p=0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations. PMID:22968580

The efficacy and feasibility of aquatic physiotherapy for people with Parkinson's disease: a systematic review.

PubMed

Terrens, Aan Fleur; Soh, Sze-Ee; Morgan, Prue Elizabeth

2017-08-09

To critically evaluate the literature regarding the efficacy and feasibility of aquatic physiotherapy in people with Parkinson's disease. Relevant studies were identified through searches in nine health-related databases. Two independent reviewers assessed study quality using either the PEDro scale or a customised tool for safety and feasibility. Database searches yielded 88 articles, of which 10 met the inclusion criteria. Studies varied greatly in methodology, quality, interventions and outcome measures. Study quality was generally low in items reporting on safety precautions, adverse events, attrition, and adherence. Results suggest that aquatic physiotherapy may have a positive effect on motor symptoms, quality of life and balance. Aquatic physiotherapy may improve aspects of motor performance, quality of life and balance in people with Parkinson's disease, however, it remains unclear whether it is a safe and feasible treatment modality. The development of standardised outcome measures for people with Parkinson's disease (unified Parkinson's disease rating scale and Parkinson's disease questionnaire-39) would aid study comparability and validate study outcomes. As safety criteria was grossly underreported, guidelines for mandatory reporting of safety criteria are essential to make conclusions regarding the feasibility of aquatic physiotherapy for people with Parkinson's disease. Implications for Rehabilitation Aquatic physiotherapy may be a beneficial treatment modality for people with Parkinson's disease. A minimum data set that includes the unified Parkinson's disease rating scale and Parkinson's disease questionnaire 39 is required to aid future meta-analysis and to allow more definitive conclusions to be made regarding aquatic physiotherapy for people with Parkinson's disease. People with Parkinson's disease are a vulnerable population, where safety within an aquatic physiotherapy program needs to be well documented and addressed.

Database for Parkinson Disease Mutations and Rare Variants

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-14-1-0097 TITLE: “ Database for Parkinson Disease Mutations and Rare Variants” PRINCIPAL INVESTIGATOR: JEFFERY M. VANCE...TO THE ABOVE ADDRESS. 1. REPORT DATE September 2016 2. REPORT TYPE FINAL 3. DATES COVERED 1 Jul 2014 – 30 Jun 2016 4. TITLE AND SUBTITLE Database ...For Parkinson Disease (PD) specifically, the variant databases currently available are incomplete, don’t assess impact and/or are not equipped to

Diet and Nutrition (Parkinson's Disease)

MedlinePlus

... Area Resources & Support PD Library Legal, Financial, & Insurance Matters Blog For Caregivers Living with Parkinson's While living ... into your diet. These include brightly colored and dark fruits and vegetables. Balance the food you eat ...

The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease

PubMed Central

Pickrell, Alicia M.; Youle, Richard J.

2015-01-01

Understanding the function of genes mutated in hereditary forms of Parkinson's disease yields insight into disease etiology and reveals new pathways in cell biology. Although mutations or variants in many genes increase the susceptibility to Parkinson's disease, only a handful of monogenic causes of Parkinsonism have been identified. Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive Parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease. PINK1 accumulates on the outer membrane of damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity and recruits Parkin to the dysfunctional mitochondrion. Then, Parkin ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy. This review covers the normal functions that PINK1 and Parkin play within cells, their molecular mechanisms of action, and the pathophysiological consequences of their loss. PMID:25611507

Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson's disease.

PubMed

Bayersdorfer, Florian; Voigt, Aaron; Schneuwly, Stephan; Botella, José A

2010-10-01

Parkinson's disease has been found to be caused by both, genetic and environmental factors. Despite the diversity of causes involved, a convergent pathogenic mechanism might underlie the special vulnerability of dopaminergic neurons in different forms of Parkinsonism. In recent years, a number of reports have proposed dopamine as a common player responsible in the loss of dopaminergic neurons independent of its etiology. Using RNAi lines we were able to generate flies with drastically reduced dopamine levels in the dopaminergic neurons. Combining these flies with a chemically induced Parkinson model (rotenone) and a familial form of Parkinson (mutant alpha-synuclein) we were able to show a strong reduction of neurotoxicity and a protection of the dopaminergic neurons when cellular dopamine levels were reduced. These results show that dopamine homeostasis plays a central role for the susceptibility of dopaminergic neurons to environmental and genetic factors in in vivo models of Parkinson disease. (c) 2010 Elsevier Inc. All rights reserved.

Semantic trouble sources and their repair in conversations affected by Parkinson's disease

PubMed Central

Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

2014-01-01

Background It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these problems become manifest in everyday conversations or how conversation partners handle such problems. Aims To describe the pragmatic problems related to the use of words that occur in everyday conversational interaction in dyads including an individual with Parkinson's disease, and to explore how interactants in conversation handle the problems to re-establish mutual understanding. Methods & Procedures Twelve video-recorded everyday conversations involving three couples where one of the individuals had Parkinson's disease were included in the study. All instances of other-initiated repair following a contribution from the people with Parkinson's disease were analysed. Those instances involving a trouble source relating to the use of words were analysed with a qualitative interaction analysis based on the principles of conversation analysis. Outcomes & Results In 70% of the instances of other-initiated repair the trouble source could be related to the semantic content produced by the individual with Parkinson's disease. The problematic contributions were typically characterized by more or less explicit symptoms of word search or use of atypical wording. The conversation partners completed the repair work collaboratively, but typically the non-impaired individual made a rephrasing or provided a suggestion for what the intended meaning had been. Conclusions & Implications In clinical work with people with Parkinson's disease and their conversation partners it is important to establish what type of trouble sources occur in conversations in a specific dyad. It may often be necessary to look beyond intelligibility and into aspects of pragmatics

Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.

PubMed

Cavanagh, James F; Mueller, Andrea A; Brown, Darin R; Janowich, Jacqueline R; Story-Remer, Jacqueline H; Wegele, Ashley; Richardson, Sarah Pirio

2017-05-01

Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to

Pramipexole in the treatment of Parkinson's disease: new developments.

PubMed

Möller, J Carsten; Oertel, Wolfgang H

2005-09-01

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

"PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

ERIC Educational Resources Information Center

Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

2010-01-01

Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

The Effects of Levodopa on Word Intelligibility in Parkinson's Disease

ERIC Educational Resources Information Center

De Letter, Miet; Santens, Patrick; Van Borsel, John

2005-01-01

Dysarthria is a common manifestation in patients with idiopathic Parkinson's disease. This study investigated the effects of levodopa on intelligibility in patients with Parkinson's disease. Ten participants were tested during on- and off-states using the Yorkston and Beukelman intelligibility test (1980). Intelligibility as scored by a panel of…

Parkinson's Disease: New Research Offers Hope for Better Diagnosis and Treatments

MedlinePlus

... of this page please turn JavaScript on. Feature: Parkinson's Disease New Research Offers Hope for Better Diagnosis and ... As many as one million Americans live with Parkinson's disease (PD), which is more than the combined number ...

Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus: A Nationwide Population-based Study.

PubMed

Liu, Feng-Cheng; Huang, Wen-Yen; Lin, Te-Yu; Shen, Chih-Hao; Chou, Yu-Ching; Lin, Cheng-Li; Lin, Kuen-Tze; Kao, Chia-Hung

2015-11-01

The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE.We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort.We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45-0.79) and adjusted HR being 0.68 (95% confidence interval 0.51-0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity.We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.

PubMed

McNeill, Alisdair; Magalhaes, Joana; Shen, Chengguo; Chau, Kai-Yin; Hughes, Derralyn; Mehta, Atul; Foltynie, Tom; Cooper, J Mark; Abramov, Andrey Y; Gegg, Matthew; Schapira, Anthony H V

2014-05-01

Gaucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased risk of developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most frequent risk factor for Parkinson's disease in the general population. Therefore there is an urgent need to understand the mechanisms by which glucocerebrosidase mutations predispose to neurodegeneration to facilitate development of novel treatments. To study this we generated fibroblast lines from skin biopsies of five patients with Gaucher disease and six heterozygous glucocerebrosidase mutation carriers with and without Parkinson's disease. Glucosylceramidase protein and enzyme activity levels were assayed. Oxidative stress was assayed by single cell imaging of dihydroethidium. Glucosylceramidase enzyme activity was significantly reduced in fibroblasts from patients with Gaucher disease (median 5% of controls, P = 0.0001) and heterozygous mutation carriers with (median 59% of controls, P = 0.001) and without (56% of controls, P = 0.001) Parkinson's disease compared with controls. Glucosylceramidase protein levels, assessed by western blot, were significantly reduced in fibroblasts from Gaucher disease (median glucosylceramidase levels 42% of control, P < 0.001) and heterozygous mutation carriers with (median 59% of control, P < 0.001) and without (median 68% of control, P < 0.001) Parkinson's disease. Single cell imaging of dihydroethidium demonstrated increased production of cytosolic reactive oxygen species in fibroblasts from patients with Gaucher disease (dihydroethidium oxidation rate increased by a median of 62% compared to controls, P < 0.001) and heterozygous mutation carriers with (dihydroethidium oxidation rate increased by a median of 68% compared with controls, P < 0.001) and without (dihydroethidium oxidation rate increased by a

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Platelet monoamine oxidase B and plasma β-phenylethylamine in Parkinson's disease

PubMed Central

Zhou, G; Miura, Y; Shoji, H; Yamada, S; Matsuishi, T

2001-01-01

OBJECTIVE—To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma β-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls.
METHODS—Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10women).
RESULTS—Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/107 platelets/30 min) than in the control group (mean 349 (SD 307) pmol/107 platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=−0.466, p<0.001).
CONCLUSIONS—The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.

 PMID:11160474

The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.

PubMed

Golabi, Pegah; Otgonsuren, Munkhzul; Sayiner, Mehmet; Arsalla, Aimal; Gogoll, Trevor; Younossi, Zobair M

HCV has been suspected to potentially cause degenerations in the central nervous system. Parkinson's disease is the second most common neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's disease among patients with HCV infection. For this study, we used Medicare database from 2005-2010. Medicare database contains information on enrollment, coverage, diagnosis recorded with International Classification of Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files, Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0. Other study variables were; age, gender, race (White and No White), and Medicare eligibility status. Simple distribution comparison by HCV status examined with t-test for numerical variables and ?2 test for categorical variables in the main analytical cohort as well as in the propensity score matched cohort. A total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was identified among over 47 million claims. Of these, 6040 patients (0.5%) were infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004) of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups matched for age, gender and race, the prevalence of Parkinson's disease was similar between HCV and Non-HCV groups (P > 0.05). This study revealed that, among Medicare population, HCV was not associated with Parkinson disease.

Rating Scales for Movement Disorders With Sleep Disturbances: A Narrative Review

PubMed Central

Rodríguez-Blázquez, Carmen; Forjaz, Maria João; Kurtis, Monica M.; Balestrino, Roberta; Martinez-Martin, Pablo

2018-01-01

Introduction: In recent years, a wide variety of rating scales and questionnaires for movement disorders have been developed and published, making reviews on their contents, and attributes convenient for the potential users. Sleep disorders are frequently present in movement disorders, and some movement disorders are accompanied by specific sleep difficulties. Aim: The aim of this study is to perform a narrative review of the most frequently used rating scales for movement disorders with sleep problems, with special attention to those recommended by the International Parkinson and Movement Disorders Society. Methods: Online databases (PubMed, SCOPUS, Web of Science, Google Scholar), related references from papers and websites and personal files were searched for information on comprehensive or global rating scales which assessed sleep disturbances in the following movement disorders: akathisia, chorea, dystonia, essential tremor, myoclonus, multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and tics and Tourette syndrome. For each rating scale, its objective and characteristics, as well as a summary of its psychometric properties and recommendations of use are described. Results: From 22 rating scales identified for the selected movement disorders, only 5 included specific questions on sleep problems. Movement Disorders Society-Unified Parkinson's Disease Rating scale (MDS-UPDRS), Non-Motor Symptoms Scale and Questionnaire (NMSS and NMSQuest), Scales for Outcomes in Parkinson's Disease (SCOPA)-Autonomic and Progressive Supranuclear Palsy Rating Scale (PSPRS) were the only rating scales that included items for assessing sleep disturbances. Conclusions: Despite sleep problems are frequent in movement disorders, very few of the rating scales addresses these specific symptoms. This may contribute to an infra diagnosis and mistreatment of the sleep problems in patients with movement disorders.

Parkinson's disease as a system-level disorder.

PubMed

Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

2016-01-01

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors.

PubMed

Henchcliffe, Claire; Schumacher, H Christian; Burgut, F Tuna

2005-11-01

Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.

Developments in impulse control behaviours of Parkinson's disease.

PubMed

Zurowski, Mateusz; O'Brien, Jonathan Darcy

2015-08-01

Impulse control behaviours (ICBs) are a frequent comorbidity for patients with Parkinson's disease. They consist of impulse control disorders, dopamine dysregulation syndrome, and punding. The field continues to evolve in the understanding of impulsivity and assessment of risk factors in the development of these behaviours and their appropriate management in patients with Parkinson's disease. Impulsivity is a multifaceted concept that is surprisingly common in untreated patients with Parkinson's disease. The incidence of ICBs increases with demographic, clinical, and biochemical risk factors. Treatments rely on reduction of dopamine agonists with exception of cognitive behavioural therapy and possibly repetitive transcranial magnetic stimulation. Reduction of dopamine agonist dose is the mainstay of treatment of ICBs. Other forms of dopaminergic treatment such as deep brain stimulation or jejunal infusion are alternative treatments but may be complicated by dopamine agonist withdrawal syndrome. Other therapies show promise but data are insufficient to suggest their regular use.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

PubMed

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right

Spotlight on rotigotine transdermal patch in Parkinson's disease.

PubMed

Sanford, Mark; Scott, Lesley J

2011-12-01

Rotigotine transdermal patch (Neupro(®)) [referred to here as rotigotine] is a non-ergolinic dopamine agonist that is available in the EU as monotherapy for the treatment of early Parkinson's disease and as combination therapy with levodopa throughout the course of the disease. Daily application of the rotigotine patch provided predictable release and absorption of rotigotine, with steady-state rotigotine concentrations reached within 1-2 days. In early Parkinson's disease, compared with placebo, rotigotine monotherapy produced significantly greater improvements in the Unified Parkinson's Disease Rating Scale summed motor and activities of daily living (ADL) scores (primary endpoint), as well as significantly higher response rates. In advanced Parkinson's disease, rotigotine in combination with levodopa reduced 'off' time (primary endpoint) and improved motor functioning and ADL significantly more than levodopa plus placebo. In patients with inadequate early morning motor control despite antiparkinsonian treatment, rotigotine improved morning motor functioning and reduced sleep disturbances, night-time motor symptoms, depressive symptoms, pain and functioning, and quality of life to a significantly greater extent than placebo. The efficacy of rotigotine relative to other treatments requires further evaluation, as there were inconsistent results in noninferiority analyses that compared rotigotine to other dopamine agonists. Rotigotine was generally well tolerated across the trials, with the most common treatment-emergent adverse events being application-site reactions, gastrointestinal disturbances, somnolence and headache. No unexpected adverse effects were observed in extension studies of up to 6 years. Thus, rotigotine offers a novel approach to the treatment of Parkinson's disease and, given its ease of administration, efficacy in reducing disabling motor and non-motor symptoms, and acceptable tolerability profile, it has the potential to be an attractive

Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders.

PubMed

Gallea, Cecile; Ewenczyk, Claire; Degos, Bertrand; Welter, Marie-Laure; Grabli, David; Leu-Semenescu, Smaranda; Valabregue, Romain; Berroir, Pierre; Yahia-Cherif, Lydia; Bertasi, Eric; Fernandez-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Benali, Habib; Poupon, Cyril; François, Chantal; Arnulf, Isabelle; Lehéricy, Stéphane; Vidailhet, Marie

2017-05-01

The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update.

PubMed

Voon, Valerie; Napier, T Celeste; Frank, Michael J; Sgambato-Faure, Veronique; Grace, Anthony A; Rodriguez-Oroz, Maria; Obeso, Jose; Bezard, Erwan; Fernagut, Pierre-Olivier

2017-03-01

Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists. These behaviours reflect the interactions of the dopaminergic medications with the individual's susceptibility, and the underlying neurobiology of Parkinson's disease. Parkinsonian rodent models show enhanced reinforcing effects of chronic dopaminergic medication, and a potential role for individual susceptibility. In patients with Parkinson's disease and impulse control disorders, impairments are observed across subtypes of decisional impulsivity, possibly reflecting uncertainty and the relative balance of rewards and losses. Impairments appear to be more specific to decisional than motor impulsivity, which might reflect differences in ventral and dorsal striatal engagement. Emerging evidence suggests impulse control disorder subtypes have dissociable correlates, which indicate that individual susceptibility predisposes towards the expression of different behavioural subtypes and neurobiological substrates. Therapeutic interventions to treat patients with Parkinson's disease and impulse control disorders have shown efficacy in randomised controlled trials. Large-scale studies are warranted to identify individual risk factors and novel therapeutic targets for these diseases. Mechanisms underlying impulse control disorders and dyskinesias could provide crucial insights into other behavioural symptoms in Parkinson's disease and addictions in the general population. Copyright © 2017 Elsevier Ltd. All rights

Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.

PubMed

Wile, Daryl J; Agarwal, Pankaj A; Schulzer, Michael; Mak, Edwin; Dinelle, Katherine; Shahinfard, Elham; Vafai, Nasim; Hasegawa, Kazuko; Zhang, Jing; McKenzie, Jessamyn; Neilson, Nicole; Strongosky, Audrey; Uitti, Ryan J; Guttman, Mark; Zabetian, Cyrus P; Ding, Yu-Shin; Adam, Mike; Aasly, Jan; Wszolek, Zbigniew K; Farrer, Matthew; Sossi, Vesna; Stoessl, A Jon

2017-05-01

People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage ( 18 F-6-fluoro-L-dopa; 18 F-FDOPA). We compared findings with those in people with sporadic Parkinson's disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson's disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, 18 F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age. Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We

French consensus procedure for assessing cognitive function in Parkinson's disease.

PubMed

Dujardin, K; Auzou, N; Lhommée, E; Czernecki, V; Dubois, B; Fradet, A; Maltete, D; Meyer, M; Pineau, F; Schmitt, E; Sellal, F; Tison, F; Vidal, T; Azulay, J-P; Welter, M-L; Corvol, J-C; Durif, F; Rascol, O

2016-11-01

One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson's Disease.

PubMed

Aroxa, Fábio Henrique de Amorim; Gondim, Ihana Thaís Guerra de Oliveira; Santos, Elba Lúcia Wanderley; Coriolano, Maria das Graças Wanderley de Sales; Asano, Amdore Guescel C; Asano, Nadja Maria Jorge

2017-01-01

There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn-Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann-Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

Quantitative Motor Performance and Sleep Benefit in Parkinson Disease.

PubMed

van Gilst, Merel M; van Mierlo, Petra; Bloem, Bastiaan R; Overeem, Sebastiaan

2015-10-01

Many people with Parkinson disease experience "sleep benefit": temporarily improved mobility upon awakening. Here we used quantitative motor tasks to assess the influence of sleep on motor functioning in Parkinson disease. Eighteen Parkinson patients with and 20 without subjective sleep benefit and 20 healthy controls participated. Before and directly after a regular night sleep and an afternoon nap, subjects performed the timed pegboard dexterity task and quantified finger tapping task. Subjective ratings of motor functioning and mood/vigilange were included. Sleep was monitored using polysomnography. On both tasks, patients were overall slower than healthy controls (night: F2,55 = 16.938, P < 0.001; nap: F2,55 = 15.331, P < 0.001). On the pegboard task, there was a small overall effect of night sleep (F1,55 = 9.695, P = 0.003); both patients and controls were on average slightly slower in the morning. However, in both tasks there was no sleep*group interaction for nighttime sleep nor for afternoon nap. There was a modest correlation between the score on the pegboard task and self-rated motor symptoms among patients (rho = 0.233, P = 0.004). No correlations in task performance and mood/vigilance or sleep time/efficiency were found. A positive effect of sleep on motor function is commonly reported by Parkinson patients. Here we show that the subjective experience of sleep benefit is not paralleled by an actual improvement in motor functioning. Sleep benefit therefore appears to be a subjective phenomenon and not a Parkinson-specific reduction in symptoms. © 2015 Associated Professional Sleep Societies, LLC.

[Cognitive and neuropsychiatric disorders in Parkinson's disease].

PubMed

Rodríguez-Constenla, I; Cabo-López, I; Bellas-Lamas, P; Cebrián, E

2010-02-08

In Parkinson's disease there are patients with isolated and multiple cognitive impairment, and their cognitive performance ranges from normal to an advanced degree of dementia. Most patients present an executive deficit, either in isolation or combined with other cognitive disorders, which is considered to be the most characteristic aspect of the disease, and 30-40% of those affected will end up with a clinically-defined dementia. The presence of a mild cognitive disorder in patients with Parkinson means that the risk of dementia appearing at some time during the development of the disease is high. The dementia associated with Parkinson's disease is specifically related with neuropsychiatric signs and symptoms, which may have three possible explanations: disorders affecting the mesolimbic pathways, diffuse limbic and cortical compromise, or associated Alzheimer-type phenomenology. Psychotic episodes tend to present more often in patients with dopaminergic treatment and the clinical spectrum of Parkinson-related psychosis covers visual illusions, visual-audio-olfactory hallucinations, delirium and severe paranoid hallucinatory psychosis. All the antiparkinsonian drugs can give rise to hallucinations and psychosis, but the dopamine agonists are the ones with the greatest capacity to do so. In managing these problems, it is crucial for prevention as well as diagnosis and treatment to be carried out as soon as they are detected. Doses of antiparkinsonian drugs must be reduced, although this is not usually enough, and so it will be necessary to associate atypical antipsychotics, which act mainly on 5-HT receptors and, in most cases, do not produce D2 blockage.

Nonmotor symptoms in a malaysian Parkinson's disease population.

PubMed

Azmin, Shahrul; Khairul Anuar, Abdul Manaf; Tan, Hui Jan; Nafisah, Wan Yahya; Raymond, Azman Ali; Hanita, Othman; Shah, Shamsul Azhar; Norlinah, Mohamed Ibrahim

2014-01-01

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson's disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson's disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0-8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (r s : 0.727, P < 0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson's disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study.

Parkinson's Law quantified: three investigations on bureaucratic inefficiency

NASA Astrophysics Data System (ADS)

Klimek, Peter; Hanel, Rudolf; Thurner, Stefan

2009-03-01

We formulate three famous, descriptive essays of Parkinson on bureaucratic inefficiency in a quantifiable and dynamical socio-physical framework. In the first model we show how the use of recent opinion formation models for small groups can be used to understand Parkinson's observation that decision-making bodies such as cabinets or boards become highly inefficient once their size exceeds a critical 'Coefficient of Inefficiency', typically around 20. A second observation of Parkinson—which is sometimes referred to as Parkinson's Law—is that the growth of bureaucratic or administrative bodies usually goes hand in hand with a drastic decrease of its overall efficiency. In our second model we view a bureaucratic body as a system of a flow of workers, who enter, become promoted to various internal levels within the system over time, and leave the system after having served for a certain time. Promotion usually is associated with an increase of subordinates. Within the proposed model it becomes possible to work out the phase diagram under which conditions of bureaucratic growth can be confined. In our last model we assign individual efficiency curves to workers throughout their life in administration, and compute the optimum time to give them the old age pension, in order to ensure a maximum of efficiency within the body—in Parkinson's words we compute the 'Pension Point'.

Constitutive expression of tdTomato protein as a cytotoxicity and proliferation marker for space radiation biology

NASA Astrophysics Data System (ADS)

Chishti, Arif A.; Hellweg, Christine E.; Berger, Thomas; Baumstark-Khan, Christa; Feles, Sebastian; Kätzel, Thorben; Reitz, Günther

2015-01-01

The radiation risk assessment for long-term space missions requires knowledge on the biological effectiveness of different space radiation components, e.g. heavy ions, on the interaction of radiation and other space environmental factors such as microgravity, and on the physical and biological dose distribution in the human body. Space experiments and ground-based experiments at heavy ion accelerators require fast and reliable test systems with an easy readout for different endpoints. In order to determine the effect of different radiation qualities on cellular proliferation and the biological depth dose distribution after heavy ion exposure, a stable human cell line expressing a novel fluorescent protein was established and characterized. tdTomato, a red fluorescent protein of the new generation with fast maturation and high fluorescence intensity, was selected as reporter of cell proliferation. Human embryonic kidney (HEK/293) cells were stably transfected with a plasmid encoding tdTomato under the control of the constitutively active cytomegalovirus (CMV) promoter (ptdTomato-N1). The stably transfected cell line was named HEK-ptdTomato-N1 8. This cytotoxicity biosensor was tested by ionizing radiation (X-rays and accelerated heavy ions) exposure. As biological endpoints, the proliferation kinetics and the cell density reached 100 h after irradiation reflected by constitutive expression of the tdTomato were investigated. Both were reduced dose-dependently after radiation exposure. Finally, the cell line was used for biological weighting of heavy ions of different linear energy transfer (LET) as space-relevant radiation quality. The relative biological effectiveness of accelerated heavy ions in reducing cellular proliferation peaked at an LET of 91 keV/μm. The results of this study demonstrate that the HEK-ptdTomato-N1 reporter cell line can be used as a fast and reliable biosensor system for detection of cytotoxic damage caused by ionizing radiation.

Adolf Hitler and His Parkinsonism.

PubMed

Bhattacharyya, Kalyan B

2015-01-01

Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality.

Experiences of fear of falling in persons with Parkinson's disease - a qualitative study.

PubMed

Jonasson, Stina B; Nilsson, Maria H; Lexell, Jan; Carlsson, Gunilla

2018-02-06

Fear of falling is common among persons with Parkinson's disease and is negatively associated with quality of life. However a lack of in-depth understanding of fear of falling as a phenomenon persists. This qualitative study aimed to explore the experiences of fear of falling in persons with Parkinson's disease. Individual interviews were performed with twelve persons with Parkinson's disease (median age 70 years, median Parkinson duration 9 years, 50% women). The interviews were semi-structured and followed a study-specific interview guide. The transcribed interviews were analyzed using qualitative content analysis. Fear of falling was experienced as a disturbing factor in everyday life. It generated a feeling of vulnerability and made daily activities and everyday environments seem potentially hazardous. Persons also missed performing previous activities. The fear of falling was a varying experience, fueled by an awareness of falls and near falls, Parkinson-related symptoms and disabilities, and by others in their environment. The persons adopted different strategies to handle their fear of falling. Activities were adapted, avoided, performed with help, or carried out despite their fear of falling. The experiences of fear of falling were complex, multifaceted and varied over time and in relation to different activities and environments. This indicates that interventions targeting fear of falling need to be individually tailored for persons with Parkinson's disease and should focus on several aspects, such as Parkinson-related symptoms and disabilities, activities and environmental factors. This study provides new information that increases the understanding of fear of falling, which has implications for researchers as well as clinicians working with persons with Parkinson's disease and fear of falling.

A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism-Dementia complex of Guam.

PubMed

Steele, John C; Wresch, Robert; Hanlon, Samuel D; Keystone, Jay; Ben-Shlomo, Yoav

2015-08-01

The aim of this work was to examine whether a linear retinal pigment epitheliopathy is associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. A total of 918 Guamanian Chamorros, with and without amyotrophic lateral sclerosis/parkinsonism-dementia complex, were examined cross-sectionally for linear retinal pigment epitheliopathy (LRPE). Overall, 239 Guamanians, who were neurologically asymptomatic, were followed for up to 20 years to determine the risk of developing amyotrophic lateral sclerosis/parkinsonism-dementia complex. The epitheliopathy was present in 59.7% (117 of 196) patients with amyotrophic lateral sclerosis/parkinsonism-dementia complex, but in only 24.7% (178 of 722) of subjects who were neurologically asymptomatic (age- and sex-adjusted risk difference: 35.0%; 95% confidence interval [CI]: 27.5-42.6; p < 0.0001). Prospectively, 15 of 50 cases with epitheliopathy developed amyotrophic lateral sclerosis/parkinsonism-dementia complex, compared to 4 of 189 cases without epitheliopathy (age- and sex-adjusted hazard ratio: 13.1; 95% CI: 4.0-43.1; P < 0.0001). Amyotrophic lateral sclerosis/parkinsonism-dementia complex is associated with an LRPE and predicts future neurological disease. Identifying the cause of this retinopathy could provide an understanding about the pathogenesis of amyotrophic lateral sclerosis/parkinsonism-dementia complex and related diseases. © 2015 International Parkinson and Movement Disorder Society.

Time-Domain Nuclear Magnetic Resonance (TD-NMR) and Chemometrics for Determination of Fat Content in Commercial Products of Milk Powder.

PubMed

Nascimento, Paloma Andrade Martins; Barsanelli, Paulo Lopes; Rebellato, Ana Paula; Pallone, Juliana Azevedo Lima; Colnago, Luiz Alberto; Pereira, Fabíola Manhas Verbi

2017-03-01

This study shows the use of time-domain (TD)-NMR transverse relaxation (T2) data and chemometrics in the nondestructive determination of fat content for powdered food samples such as commercial dried milk products. Most proposed NMR spectroscopy methods for measuring fat content correlate free induction decay or echo intensities with the sample's mass. The need for the sample's mass limits the analytical frequency of NMR determination, because weighing the samples is an additional step in this procedure. Therefore, the method proposed here is based on a multivariate model of T2 decay, measured with Carr-Purcell-Meiboom-Gill pulse sequence and reference values of fat content. The TD-NMR spectroscopy method shows high correlation (r = 0.95) with the lipid content, determined by the standard extraction method of Bligh and Dyer. For comparison, fat content determination was also performed using a multivariate model with near-IR (NIR) spectroscopy, which is also a nondestructive method. The advantages of the proposed TD-NMR method are that it (1) minimizes toxic residue generation, (2) performs measurements with high analytical frequency (a few seconds per analysis), and (3) does not require sample preparation (such as pelleting, needed for NIR spectroscopy analyses) or weighing the samples.

Pathological synchronization in Parkinson's disease: networks, models and treatments.

PubMed

Hammond, Constance; Bergman, Hagai; Brown, Peter

2007-07-01

Parkinson's disease is a common and disabling disorder of movement owing to dopaminergic denervation of the striatum. However, it is still unclear how this denervation perverts normal functioning to cause slowing of voluntary movements. Recent work using tissue slice preparations, animal models and in humans with Parkinson's disease has demonstrated abnormally synchronized oscillatory activity at multiple levels of the basal ganglia-cortical loop. This excessive synchronization correlates with motor deficit, and its suppression by dopaminergic therapies, ablative surgery or deep-brain stimulation might provide the basic mechanism whereby diverse therapeutic strategies ameliorate motor impairment in patients with Parkinson's disease. This review is part of the INMED/TINS special issue, Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

PubMed

Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

2017-04-01

Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

[Cell therapy for Parkinson's disease: IV. Risks and future trends].

PubMed

Anisimov, S V

2009-01-01

Motor dysfunctions in Parkinson's disease are believed to be primarily due to the degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Numerous cell replacement therapy approaches have been developed and tested, including these based on donor cell transplantation (embryonic and adult tissue-derived), adult mesenchymal stem cells (hMSCs)-, neural stem cells (hNSCs)- and finally human embryonic stem cells (hESCs)-based. Despite the progress achieved, numerous difficulties prevent wider practical application of stem cell-based therapy approaches for the treatment of Parkinson's disease. Among the latter, ethical, safety and technical issues stand out. Current series of reviews (Cell therapy for Parkinson's disease: I. Embryonic and adult donor tissue-based applications; II. Adult stem cell-based applications; III. Neonatal, fetal and embryonic stem cell-based applications; IV. Risks and future trends) aims providing a balanced and updated view on various issues associated with cell types (including stem cells) in regards to their potential in the treatment of Parkinson's disease. Essential features of the individual cell subtypes, principles of available cell handling protocols, transplantation, and safety issues are discussed extensively.

Anaesthesia for Caesarean section in a patient with Parkinson's disease.

PubMed

Ward, V D

2018-05-01

Parkinson's disease is prevalent worldwide but mainly affects the elderly and is rarely seen in women of child-bearing age. The clinical signs and symptoms, the physiological changes of pregnancy, and drug interactions, pose unique challenges for the anaesthetic management of patients with Parkinson's disease who present for delivery. A 36-year-old primigravid woman at 36 weeks' gestation, with Parkinson's disease, presented for pre-anaesthesia assessment prior to elective caesarean section. Her Parkinson's disease had been diagnosed four years previously and was treated with Sinemet (levodopa/carbidopa) and pramipexole. Despite maximum allowable drug doses in pregnancy, she reported disease progression, with right-sided weakness in the upper and lower limbs and an altered gait. Spinal anaesthesia for elective Caesarean section was performed in the sitting position, using 0.5% hyperbaric bupivacaine, morphine 150 µg and fentanyl 25 µg. The anaesthesia and Caesarean section were uneventful. She was discharged home with a healthy baby on the fourth postoperative day. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Parkinson's disease death rate: carbidopa and vitamin B6.

PubMed

Hinz, Marty; Stein, Alvin; Cole, Ted

2014-01-01

The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa)-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.

Measuring the Burden of Hospitalization in Patients with Parkinson´s Disease in Spain.

PubMed

Gil-Prieto, Ruth; Pascual-Garcia, Raquel; San-Roman-Montero, Jesus; Martinez-Martin, Pablo; Castrodeza-Sanz, Javier; Gil-de-Miguel, Angel

2016-01-01

This epidemiological survey estimates the hospitalization burden related to Parkinson´s Disease in Spain. This observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalizations of patients with Parkinson´s disease that were reported from 1997-2012 were analyzed. Codes were selected using the 9th International Classification of Diseases: ICD-9-CM: 332.0. A total of 438,513 hospital discharges of patients with Parkinson´s Disease were reported during the study period. The annual hospitalization rate was 64.2 cases per 100,000. The average length of hospital stay was 10 days. The trend for the annual hospitalization rate differed significantly depending on whether Parkinson´s disease was the main cause of hospitalization (n = 23,086, 1.14% annual increase) or was not the main cause of hospitalization (n = 415,427, 15.37% annual increase). The overall case-fatality rate among hospitalized patients was 10%. The case fatality rate among patient´s hospitalized with Parkinson´s disease as the main cause of hospitalization was 2.5%. The hospitalization rate and case-fatality rate significantly increased with age. The primary causes of hospitalization when Parkinson´s disease was not coded as the main cause of hospitalization were as follows: respiratory system diseases (24%), circulatory system diseases (19%), injuries and poisoning, including fractures (12%), diseases of the digestive system (10%) and neoplasms (5%). The annual average cost for National Health Care System was € 120 M, with a mean hospitalization cost of €4,378. Parkinson´s disease poses a significant health threat in Spain, particularly in the elderly. While hospitalizations due to Parkinson´s Disease are relatively stable over time, the number of patients presenting with Parkinson´s disease as an important comorbidity has increased dramatically. Medical staff must

Stereochemical and conformational study on fenoterol by ECD spectroscopy and TD-DFT calculations.

PubMed

Tedesco, Daniele; Zanasi, Riccardo; Wainer, Irving W; Bertucci, Carlo

2014-03-01

Fenoterol and its derivatives are selective β2-adrenergic receptor (β2-AR) agonists whose stereoselective biological activities have been extensively investigated in the past decade; a complete stereochemical characterization of fenoterol derivatives is therefore crucial for a better understanding of the effects of stereochemistry on β2-AR binding. In the present project, the relationship between chiroptical properties and absolute stereochemistry of the stereoisomers of fenoterol (1) was investigated by experimental ECD spectroscopy and time-dependent density functional theory (TD-DFT). DFT geometry optimizations were carried out at the RI-B97D/TZVP/IEFPCM(MeOH) level and subsequent TD-DFT calculations were performed using the PBE0 hybrid functional. Despite the large pool of equilibrium conformers found for the investigated compounds and the known limitations of the level of theory employed, the computational protocol was able to reproduce the experimental ECD spectra of the stereoisomers of 1. The main contribution to the overall chiroptical properties was found to arise from the absolute configuration of the chiral center in α-position to the resorcinol moiety. Based on this evidence, a thorough conformational analysis was performed on the optimized DFT conformers, which revealed the occurrence of a different equilibrium between conformational patterns for the diastereomers of fenoterol: the (R,R')/(S,S') enantiomeric pair showed a higher population of folded conformations than the (R,S')/(S,R') pair. Copyright © 2013 Elsevier B.V. All rights reserved.

Pharmacological therapy of Parkinson's disease: current options and new avenues.

PubMed

Simola, Nicola; Pinna, Annalisa; Fenu, Sandro

2010-11-01

Parkinson's disease is a neurodegenerative pathology which affects the dopaminergic neurons in the mesencephalon, leading to a progressive and relentless motor disability and to non-motor symptoms of different severity. The aim of this review is to summarize the features of drugs currently used in the pharmacotherapy of Parkinson's disease, with a look at their beneficial effects and limitations. Drugs acting on dopamine transmission, as L-DOPA, direct dopaminergic agonists, inhibitors for either the MAO or COMT enzymes and drugs acting on neurotransmitters other than dopamine (e.g. acetylcholine, glutamate) will be covered. Investigational drugs currently under examination for their therapeutic potential in Parkinson's disease and recent patents which may be relevant to the field will be also discussed.

Laboratory Measurements of Isoprene-Derived Nitrates Using TD-LIF

NASA Astrophysics Data System (ADS)

Cohen, R.; Perring, A.; Wooldridge, P.; Shepson, P.; Lockwood, A.; Hill, K.; Moffat, C.; Mielke, L.; Cavender, A.; Stevens, P.; Dusanter, S.; Vimal, D.; Wisthaler, A.; Graus, M.

2006-12-01

Isoprene represents the largest flux of reactive non-methane hydrocarbon to the atmosphere and the production of isoprene-derived nitrates is currently one of the major controversies in nitrogen oxide chemistry. Alkyl and multifunctional nitrates (ΣANs), measured by Thermal Dissociation Laser Induced Fluorescence (TD-LIF), have been observed as a significant NOy component during many ground-based and airborne field experiments. A strong hypothesis is that many of these nitrates, especially in forest- impacted environments, are isoprene-derived. We present smog chamber measurements (made at Purdue University in June of 2006) of ΣANs, produced through both NO3 and OH-initiated oxidation of isoprene. Isoprene, OH, HO2, NO, NO2, NOy, PAN, HNO3 and speciated first generation isoprene nitrates were also measured simultaneously and chamber chemistry was subsequently modeled. We compare these measurements with previous measurements of isoprene nitrate yields and examine the relative contribution of secondary nitrates to the measured total organic nitrate concentrations.

Stem cell transplantation for treating Parkinson's disease: Literature analysis based on the Web of Science.

PubMed

Li, Runhui

2012-06-05

To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items; (c) year of publication: 2002-2011. (a) articles that required manual searching or telephone access; (b) we excluded documents that were not published in the public domain; (c) we excluded a number of corrected papers from the total number of articles. (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to subject areas; (5) distribution according to country; (6) distribution according to institution; (7) comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease; (8) comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease in the Web of Science from 2002 to 2011; (9) comparison of studies on stem cell transplantation from different cell sources for treating Parkinson's disease. In total, 1 062 studies on stem cell transplantation for treating Parkinson's disease appeared in the Web of Science from 2002 to 2011, almost one third of which were from American authors and institutes. The number of studies on stem cell transplantation for treating Parkinson's disease had gradually increased over the past 10 years. Papers on stem cell transplantation for treating Parkinson's disease appeared in journals such as Stem Cells and

77 FR 50549 - Agency Information Collection: Emergency Submission for OMB Review (Telehealth in the Parkinson's...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... Collection: Emergency Submission for OMB Review (Telehealth in the Parkinson's Disease Research, Education... needed to improve the care and clinical outcomes of patients with Parkinson's disease. DATES: Comments... Parkinson's Disease Research, Education and Clinical Center (PADRECC): The Key to the Patient-Centered...

Efficacy of community-based physiotherapy networks for patients with Parkinson's disease: a cluster-randomised trial.

PubMed

Munneke, Marten; Nijkrake, Maarten J; Keus, Samyra Hj; Kwakkel, Gert; Berendse, Henk W; Roos, Raymund Ac; Borm, George F; Adang, Eddy M; Overeem, Sebastiaan; Bloem, Bastiaan R

2010-01-01

Many patients with Parkinson's disease are treated with physiotherapy. We have developed a community-based professional network (ParkinsonNet) that involves training of a selected number of expert physiotherapists to work according to evidence-based recommendations, and structured referrals to these trained physiotherapists to increase the numbers of patients they treat. We aimed to assess the efficacy of this approach for improving health-care outcomes. Between February, 2005, and August, 2007, we did a cluster-randomised trial with 16 clusters (defined as community hospitals and their catchment area). Clusters were randomly allocated by use of a variance minimisation algorithm to ParkinsonNet care (n=8) or usual care (n=8). Patients were assessed at baseline and at 8, 16, and 24 weeks of follow-up. The primary outcome was a patient preference disability score, the patient-specific index score, at 16 weeks. Health secondary outcomes were functional mobility, mobility-related quality of life, and total societal costs over 24 weeks. Analysis was by intention to treat. This trial is registered, number NCT00330694. We included 699 patients. Baseline characteristics of the patients were comparable between the ParkinsonNet clusters (n=358) and usual-care clusters (n=341). The primary endpoint was similar for patients within the ParkinsonNet clusters (mean 47.7, SD 21.9) and control clusters (48.3, 22.4). Health secondary endpoints were also similar for patients in both study groups. Total costs over 24 weeks were lower in ParkinsonNet clusters compared with usual-care clusters (difference euro727; 95% CI 56-1399). Implementation of ParkinsonNet networks did not change health outcomes for patients living in ParkinsonNet clusters. However, health-care costs were reduced in ParkinsonNet clusters compared with usual-care clusters. ZonMw; Netherlands Organisation for Scientific Research; Dutch Parkinson's Disease Society; National Parkinson Foundation; Stichting Robuust

Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis.

PubMed

Tomlinson, Claire L; Patel, Smitaa; Meek, Charmaine; Herd, Clare P; Clarke, Carl E; Stowe, Rebecca; Shah, Laila; Sackley, Catherine; Deane, Katherine H O; Wheatley, Keith; Ives, Natalie

2012-08-06

To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease. Systematic review and meta-analysis of randomised controlled trials. Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson's disease rating scale (in which one trial was found to be the cause of the heterogeneity). Physiotherapy has short term benefits in Parkinson's disease. A wide range of physiotherapy techniques

The characteristics of autonomic nervous system disorders in burning mouth syndrome and Parkinson disease.

PubMed

Koszewicz, Magdalena; Mendak, Magdalena; Konopka, Tomasz; Koziorowska-Gawron, Ewa; Budrewicz, Sławomir

2012-01-01

To conduct a clinical electrophysiologic evaluation of autonomic nervous system functions in patients with burning mouth syndrome and Parkinson disease and estimate the type and intensity of the autonomic dysfunction. The study involved 83 subjects-33 with burning mouth syndrome, 20 with Parkinson disease, and 30 controls. The BMS group included 27 women and 6 men (median age, 60.0 years), and the Parkinson disease group included 15 women and 5 men (median age, 66.5 years). In the control group, there were 20 women and 10 men (median age, 59.0 years). All patients were subjected to autonomic nervous system testing. In addition to the Low autonomic disorder questionnaire, heart rate variability (HRV), deep breathing (exhalation/inspiration [E/I] ratio), and sympathetic skin response (SSR) tests were performed in all cases. Parametric and nonparametric tests (ANOVA, Kruskal-Wallis, and Scheffe tests) were used in the statistical analysis. The mean values for HRV and E/I ratios were significantly lower in the burning mouth syndrome and Parkinson disease groups. Significant prolongation of SSR latency in the foot was revealed in both burning mouth syndrome and Parkinson disease patients, and lowering of the SSR amplitude occurred in only the Parkinson disease group. The autonomic questionnaire score was significantly higher in burning mouth syndrome and Parkinson disease patients than in the control subjects, with the Parkinson disease group having the highest scores. In patients with burning mouth syndrome, a significant impairment of both the sympathetic and parasympathetic nervous systems was found but sympathetic/parasympathetic balance was preserved. The incidence and intensity of autonomic nervous system dysfunction was similar in patients with burning mouth syndrome and Parkinson disease, which may suggest some similarity in their pathogeneses.

The medical treatment of Parkinson disease from James Parkinson to George Cotzias.

PubMed

Fahn, Stanley

2015-01-01

It took exactly 150 years since James Parkinson's description in 1817 of the illness bearing his name until the development of effective therapy for this disorder, namely, the introduction of high-dosage levodopa by George Cotzias in 1967. During the first 50 years, no effective therapy was available, but neurologists reported using different agents, including metals. Then, around 1867, Charcot found solanaceous alkaloids to be somewhat helpful, and these became the accepted and popular therapy for the next 75 years. When basic scientists discovered that these alkaloids had central antimuscarinic activity, pharmaceutical chemists developed synthetic chemical agents that were equally effective, with possibly less adverse effects, and around 1950 these synthetic drugs became the standard medical therapy for Parkinson's disease (PD). The link between dopamine and PD did not take place until 1957, 140 years after Parkinson's Essay. The clue came from research on reserpine, a drug derived from the Rauwolfia plant that caused a sedative effect, now recognized as a drug-induced parkinsonian state. Initial investigations revealed that reserpine caused the release and depletion of serotonin stores in the brain. With that knowledge, Arvid Carlsson, a young pharmacologist in Sweden, decided to explore the possibility that reserpine might also affect brain catecholamines. In his now famous, elegant, and simple experiment, he showed that injecting l-dopa, the precursor of catecholamines, alleviated the reserpine-induced parkinsonian state in animals, whereas the precursor of serotonin failed to do so. Carlsson then developed a highly sensitive assay to measure dopamine, and his lab found that dopamine is selectively present in high concentrations in the striatum and that administered l-dopa could restore the dopamine depleted by reserpine. Carlsson postulated that all these findings implicate dopamine in motor disorders. Oleh Hornykiewicz, a young pharmacologist in Vienna, on

Orthostatic hypotension acutely impairs executive functions in Parkinson's disease.

PubMed

Sforza, Michela; Assogna, Francesca; Rinaldi, Domiziana; Sette, Giuliano; Tagliente, Stefania; Pontieri, Francesco E

2018-04-07

Orthostatic hypotension is a frequent non-motor symptom of Parkinson's disease, with negative prognostic role on cognitive functions. Here we measured the acute effects of orthostatic hypotension on executive functions in Parkinson's disease patients devoid of hypertension, carotid artery stenosis, and significant chronic cerebrovascular pathology. Measurements were carried out during regular visits in outpatient setting. Twenty-eight Parkinson's disease patients were recruited and studied along scheduled outpatient visits. They were divided into two groups (n = 14 each) based on the presence or lack of orthostatic hypotension. This was diagnosed according to international guidelines. All patients were submitted to the Stroop's test and to the phonological and semantic verbal fluency test after 10-min resting in supine position and immediately upon standing in upright position. Testing lasted less than 5 min in either position. In upright position, subjects with orthostatic hypotension displayed significantly worse performances at the Stroop's test word reading time (22.1 ± 4.1 vs. 14.9 ± 4.0 s), interference time (56.1 ± 12.3 vs. 41.4 ± 11.8 s), and number of errors at the interference section (5.8 ± 3.2 vs. 1.3 ± 2.1) as compared to those without orthostatic hypotension. These results demonstrate that worsening of attentive function upon standing can be measured in Parkinson's disease patients with orthostatic hypotension during routine outpatient visits. These findings suggest that clinically asymptomatic orthostatic hypotension in Parkinson's disease patients may acutely worsen neuropsychological performances with possible negative impact on daily functioning.

Risk of Parkinson's disease following zolpidem use: a retrospective, population-based cohort study.

PubMed

Huang, Hui-Chun; Tsai, Chon-Haw; Muo, Chih-Hsin; Lin, Kang-Hsu; Lu, Ming-Kuei; Sung, Fung-Chang; Kao, Chia-Hung

2015-01-01

To evaluate the influence of long-term zolpidem use on the incidence of developing Parkinson's disease. 2,961 subjects who used zolpidem for the first time longer than 3 months between 1998 and 2000 were identified in the National Health Insurance system of Taiwan. Subjects without a history of zolpidem use were randomly selected as a comparison cohort and frequency matched to zolpidem users based on age, sex, and index date. The diagnosis of Parkinson's disease was based on the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification. Its incidence until the end of 2009 was calculated and its hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models and Kaplan-Meier analysis. The overall incidence of Parkinson's disease was greater among zolpidem users than in the comparison cohort (HR = 1.88; 95% CI, 1.45-2.45). However, there was no difference in Parkinson's disease incidence between these 2 cohorts after 5 years of observation. The risk of Parkinson's disease increased with increasing zolpidem dose, with an HR of 0.70 for low-dose users (< 400 mg/y) and 2.94 for high-dose users (≥ 1,600 mg/y). The incidence of Parkinson's disease was greater in subjects using zolpidem only (HR = 2.35; 95% CI, 1.66-3.33) compared to those using benzodiazepines only (HR = 1.31; 95% CI, 0.91-1.90). By stratified analysis, zolpidem use with concurrent depression (HR = 4.79) increased the risk of Parkinson's disease compared to that of zolpidem users without concurrent depression. Zolpidem use might unmask preclinical Parkinson's disease, especially in patients with depression. However, large population-based, unbiased, randomized trials are warranted to confirm this finding. © Copyright 2015 Physicians Postgraduate Press, Inc.

Living with advanced Parkinson's disease: a constant struggle with unpredictability.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2011-02-01

This paper is a report of an exploration of patients' lifeworld and way of managing life with advanced Parkinson's disease prior to Deep Brain Stimulation and what they expect from life following this treatment. Parkinson's disease is a progressive neurodegenerative disease, which is initially well-treated with L-dopa. Living with Parkinson's disease means living with the experience of continuous loss of independence and self-esteem and unpredictable ON/OFF phenomena. Thus, in the advanced stage of the disease, treatment with Deep Brain Stimulation may become relevant. Eleven patients eligible for Deep Brain Stimulation were interviewed prior to treatment. Data were collected in 2007 and analysed according to the hermeneutic phenomenological methodology of van Manen, using the four existentials as analytic tools. Living with advanced Parkinson's disease can be described as the experience of living with and managing unpredictability. The disease gradually took over, and participants had to struggle with unpredictability on a daily basis. Themes in relation to this were: The body - setting the agenda, Always a struggle to be on time, Living in dependence and compromise - being a burden, and Living with restrained space and changes in social life. Parkinson's disease leads to profound bodily restrictions. Living with an unpredictable body affects all aspects of life, and nurses need to be aware of the impact the disease has on the entire lifeworld, and how this may affect the way treatment is perceived. © 2010 Blackwell Publishing Ltd.

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

PubMed

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions.

PubMed

Heumann, Rolf; Moratalla, Rosario; Herrero, Maria Trinidad; Chakrabarty, Koushik; Drucker-Colín, René; Garcia-Montes, Jose Ruben; Simola, Nicola; Morelli, Micaela

2014-08-01

Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarizes the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including dopamine-cAMP-regulated neuronal phosphoprotein, extracellular signal-regulated kinase, mammalian target of rapamycin, mitogen and stress-activated kinase-1 and Histone H3 are summarized, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity and animal behavioral results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non-pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease-associated motor symptoms, especially the development of dyskinesia. This review aims at summarizing the key molecular mechanisms underlying dyskinesia and the most recent therapeutic advances to treat Parkinson's disease with emphasis on non-pharmacological interventions such as physical activity, deep brain stimulation (DBS), transcranial magnetic field stimulation (TMS) and cell replacement therapy. These new interventions are discussed from both the experimental and clinical point of view, describing their current strength and limitations. © 2014 International Society for Neurochemistry.

"Think positively": Parkinson's disease, biomedicine, and hope in contemporary Germany.

PubMed

Metzler, Ingrid; Just, Paul

2017-06-01

Narratives of hope shape contemporary engagements with Parkinson's disease. On the one hand, a "biomedical narrative of hope" promises that biomedical research will help to transform this treatable but incurable disease into a curable one in the future. On the other hand, a more individual "illness narrative of hope" encourages patients to influence the course of Parkinson's disease by practicing self-care and positive thinking. This article asks how these two narratives of hope interact. It bases its argument on an analysis of data from 13 focus groups conducted in Germany in 2012 and 2014 with patients with Parkinson's disease and their relatives. Participants were asked to have their say on clinical trials for advanced therapies for Parkinson's disease and, while doing so, envisioned their biosocial selves in the present and the future. Three "modes of being" for patients were drawn from this body of data: a "users on stand-by" mode, an "unengaged" mode, and an "experimental pioneers" mode. Both narratives of hope were important to all three modes, yet they were mobilized at different frequencies and also had different statuses. While the biomedical narrative of hope was deemed an important "dream of the future" that participants passively supported without having to make it their own, the illness narrative of hope was a truth discourse that took an imperative form: having Parkinson's disease implied the need to maintain a positive attitude.

[Inferior frontal region hypoperfusion in Parkinson disease with dementia].

PubMed

Ochudło, Stanisław; Opala, Grzegorz; Jasińska-Myga, Barbara; Siuda, Joanna; Nowak, Stanisław

2003-01-01

Dementia is more frequent in patients suffering from Parkinson's disease (PD) then in general population. The mechanism for mental deterioration in PD remains controversial. The aim of our study was comparison of the regional cerebral perfusion quantified by single photon emission computed tomography in patients suffering from idiopathic Parkinson's disease with and without dementia. We examined 49 PD patients: 22 PD patients with dementia and 27 PD patients without dementia. Dementia was recognized according to ICD-10 and DSM-IV criteria. Cognitive functions were executed by means of the Mini Mental State Examination (MMSE) and neuropsychological assessment. The Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn & Yahr Scale was used to quantify the severity of PD. SPECT was performed with Siemens Diacam single--head rotating gamma camera after intravenous application of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO). The perfusion values were expressed as cortical or basal ganglia regions of interest (ROIs)/cerebellum activity ratios. In both examined group of patients the lowest uptake was in basal ganglia region, while the highest uptake was in occipital region. In the subgroup of PD patients with dementia significant hypoperfusion affecting the inferior frontal cortices was observed. In Parkinson's disease with dementia hypoperfusion in inferior frontal region can be found.

Everyday Cognitive Failures and Memory Problems in Parkinson's Patients without Dementia

ERIC Educational Resources Information Center

Poliakoff, Ellen; Smith-Spark, James H.

2008-01-01

There is growing evidence that Parkinson's disease patients without dementia exhibit cognitive deficits in some executive, memory and selective attention tasks. However, the impact of these deficits on their everyday cognitive functioning remains largely unknown. This issue was explored using self-report questionnaires. Twenty-four Parkinson's…

Role of Neurotrophic Factors in Parkinson's Disease.

PubMed

Tome, Diogo; Fonseca, Carla Pais; Campos, Filipa Lopes; Baltazar, Graca

2017-01-01

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Technology in Parkinson's disease: Challenges and opportunities.

PubMed

Espay, Alberto J; Bonato, Paolo; Nahab, Fatta B; Maetzler, Walter; Dean, John M; Klucken, Jochen; Eskofier, Bjoern M; Merola, Aristide; Horak, Fay; Lang, Anthony E; Reilmann, Ralf; Giuffrida, Joe; Nieuwboer, Alice; Horne, Malcolm; Little, Max A; Litvan, Irene; Simuni, Tanya; Dorsey, E Ray; Burack, Michelle A; Kubota, Ken; Kamondi, Anita; Godinho, Catarina; Daneault, Jean-Francois; Mitsi, Georgia; Krinke, Lothar; Hausdorff, Jeffery M; Bloem, Bastiaan R; Papapetropoulos, Spyros

2016-09-01

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder

Adolf Hitler and His Parkinsonism

PubMed Central

Bhattacharyya, Kalyan B.

2015-01-01

Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality. PMID:26713007

Electroconvulsive therapy in Parkinson's disease.

PubMed

Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

2015-10-01

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome.

PubMed

Hill-Burns, Erin M; Debelius, Justine W; Morton, James T; Wissemann, William T; Lewis, Matthew R; Wallen, Zachary D; Peddada, Shyamal D; Factor, Stewart A; Molho, Eric; Zabetian, Cyrus P; Knight, Rob; Payami, Haydeh

2017-05-01

There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD. The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation. PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society. © 2017

The Identification of Alpha-Synuclein as the First Parkinson Disease Gene

PubMed Central

Nussbaum, Robert L.

2017-01-01

In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey’s observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein’s role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide. PMID:28282812

The Identification of Alpha-Synuclein as the First Parkinson Disease Gene.

PubMed

Nussbaum, Robert L

2017-01-01

In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey's observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein's role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide.

The use of rasagiline in Parkinson's disease.

PubMed

Schapira, A H V

2006-01-01

Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B developed for the symptomatic treatment of Parkinson's disease. The drug has shown efficacy in improving motor features in both early and advanced Parkinson's disease patients. The drug appears to be well tolerated and its once daily fixed dose formulation should make for excellent compliance. Rasagiline has also demonstrated important neuroprotective properties in both in vitro and in vivo laboratory studies. A provisional study of neuroprotection in a delayed start clinical trial of early PD patients has also suggested that this benefit may be translated to the clinic. Additional clinical trials are underway to confirm this.

[Dopamine agonists--clinical applications beyond Parkinson's disease].

PubMed

Kuran, Włodzimierz

2007-01-01

Contemporary experience and results of clinical trials concerning dopamine agonist application in the treatment of many different diseases (apart from Parkinson's disease) are presented in the paper. A basic clinical recommendation for agonists is restless legs syndrome. In this syndrome almost all agonists give a considerable subjective and objective improvement. Treatment of atypical parkinsonism (MSA, PSP, CBD) in the majority of patients is ineffective. The author also presents promising results of treatment with agonists in such diverse diseases as hyperkinetic syndromes, cocaine dependence, drug-resistant depression and erectile dysfunction (apomorphine). Dopamine partial agonists (e.g. aripiprazol) are recommended in the modern treatment of schizophrenia.

Development of Parkinson Patient Generated Data Collection Platform Using FHIR and IoT Devices.

PubMed

Kim, Dae-Young; Hwang, Sun-Ho; Kim, Min-Gyu; Song, Joon-Hyun; Lee, Sin-Woong; Kim, Il Kon

2017-01-01

Internet of Things (IoT) devices can be effectively used in cases where continuous observation of patients is required, such as Parkinson's disease. This is due to the characteristics of the IoT (Internet of Things), which allows data to be measured and transmitted at any time, anywhere. In this study, we developed a health data collection platform that stores and transmits the foot pressure data of Parkinson patients using FHIR (Fast Healthcare Interoperability Resources). The platform can be used to collect the foot pressure of a large number of Parkinson's patients. Based on the accumulated data, it is possible to identify abnormal behaviors such as walking pattern, tilt and instability of stride length in patients with Parkinson's disease. Based on the results of this study, accurate diagnosis and treatment of Parkinson's disease can be made.

Increased muscle belly and tendon stiffness in patients with Parkinson's disease, as measured by myotonometry.

PubMed

Marusiak, Jarosław; Jaskólska, Anna; Budrewicz, Sławomir; Koszewicz, Magdalena; Jaskólski, Artur

2011-09-01

Based on Davis's law, greater tonus of the muscle belly in individuals with Parkinson's disease can create greater tension in the tendon, leading to structural adjustment and an increase in tendon stiffness. Our study aimed to separately assess passive stiffness in the muscle belly and tendon in medicated patients with Parkinson's disease, using myotonometry. We tested 12 patients with Parkinson's disease and 12 healthy matched controls. Passive stiffness of muscle belly and tendon was estimated by myotonometry, electromyography, and mechanomyography in relaxed biceps and triceps brachii muscles. Compared with controls, patients with Parkinson's disease had higher stiffness in the muscle belly and tendon of the biceps brachii and in the tendon of the triceps brachii. In patients with Parkinson's disease, there was a positive correlation between muscle belly stiffness and parkinsonian rigidity in the biceps brachii. Patients with Parkinson's disease have higher passive stiffness of the muscle belly and tendon than healthy matched controls. Copyright © 2011 Movement Disorder Society.

Parkinson's Disease Diagnostic Observations (PADDO): study rationale and design of a prospective cohort study for early differentiation of parkinsonism.

PubMed

van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Meijer, Frederick J A; Verbeek, Marcel M; Bloem, Bastiaan R

2018-05-16

Differentiation of Parkinson's disease (PD) from the various types of atypical parkinsonism (AP) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS) and vascular parkinsonism (VP), can be challenging, especially early in the disease course when symptoms overlap. A major unmet need in the diagnostic workup of these disorders is a diagnostic tool that differentiates the various disorders, preferably in the earliest disease stages when the clinical presentation is similar. Many diagnostic tests have been evaluated, but their added value was studied mostly in retrospective case-control studies that included patients with a straightforward clinical diagnosis. Here, we describe the design of a prospective cohort study in patients with parkinsonism in an early disease stage who have an uncertain clinical diagnosis. Our aim is to evaluate the diagnostic accuracy of (1) detailed clinical examination by a movement disorder specialist, (2) magnetic resonance imaging (MRI) techniques and (3) cerebrospinal fluid (CSF) biomarkers. Patients with parkinsonism with an uncertain clinical diagnosis and a disease course less than three years will be recruited. Patients will undergo extensive neurological examination, brain MRI including conventional and advanced sequences, and a lumbar puncture. The diagnosis (including level of certainty) will be defined by a movement disorders expert, neuroradiologist and neurochemist based on clinical data, MRI results and CSF results, respectively. The clinical diagnosis after three years' follow-up will serve as the "gold standard" reference diagnosis, based on consensus criteria and as established by two movement disorder specialists (blinded to the test results). Diagnostic accuracy of individual instruments and added value of brain MRI and CSF analysis after evaluation by a movement disorder expert will be calculated, expressed as the change in percentage of

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PubMed

von Coelln, Rainer; Shulman, Lisa M

2016-12-01

Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

PubMed

Santiago, Jose A; Potashkin, Judith A

2013-01-01

Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

Quality of life in patients with Parkinson's disease: development of a questionnaire.

PubMed Central

de Boer, A G; Wijker, W; Speelman, J D; de Haes, J C

1996-01-01

OBJECTIVES--To develop and test a questionnaire for measuring quality of life in patients with Parkinson's disease. METHODS--An item pool was developed based on the experience of patients with Parkinson's disease and of neurologists; medical literature on the problems of patients with Parkinson's disease; and other quality of life questionnaires. To reduce the item pool, 13 patients identified items that were a problem to them and rated their importance. Items which were most often chosen and rated most important were included in the Parkinson's disease quality of life questionnaire (PDQL). The PDQL consists of 37 items. To evaluate the discriminant validity of the PDQL three groups of severity of disease were compared. To test for convergent validity, the scores of the PDQL were tested for correlation with standard indices of quality of life. RESULTS--The PDQL was filled out by 384 patients with Parkinson's disease. It consisted of four subscales: parkinsonian symptoms, systemic symptoms, emotional functioning, and social functioning. The internal-consistency reliability coefficients of the PDQL subscales were high (0.80-0.87). Patients with higher disease severity had significantly lower quality of life on all PDQL subscales (P < 0.05). Almost all PDQL subscales correlated highly (P < 0.001) with the corresponding scales of the standard quality of life indices. CONCLUSION--The PDQL is a relevant, reliable, and valid measure of the quality of life of patients with Parkinson's disease. Images PMID:8676165

Impulse control disorders are associated with multiple psychiatric symptoms in Parkinson's disease.

PubMed

Jaakkola, Elina; Kaasinen, Valtteri; Siri, Chiara; Martikainen, Kirsti; Cilia, Roberto; Niemelä, Solja; Joutsa, Juho

2014-01-01

Impulse control disorders can have serious adverse consequences to the life of a patient with Parkinson's disease. Although impulse control disorders are common, a possible psychiatric comorbidity has not been fully characterized. The aim of this study was to investigate the psychiatric symptoms exhibited by Parkinson's disease patients with impulse control disorders. The study was conducted as a postal survey to patients in the registry of the Finnish Parkinson Association. A total of 290 Parkinson's disease patients were evaluated for impulse control disorders using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Psychiatric symptoms were systematically screened using the Symptom Checklist 90. We found that 108 of the evaluated patients had one or more impulse control disorders. Patients with impulse control disorders had markedly higher scores for symptoms of psychoticism (Bonferroni corrected p < 0.001), interpersonal sensitivity (p < 0.001), obsessive-compulsive disorder (p < 0.001), and depression (p = 0.01) when compared with patients without impulse control disorders. Impulse control disorders were shown to be independently associated with these symptoms. Patients with multiple impulse control disorders had higher scores for depression and obsessive-compulsive symptoms when compared with patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our results confirm the previous observations that impulse control disorders in Parkinson's disease are linked with multiple psychiatric symptoms, including psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and depression. Clinicians treating these patients should acknowledge the concomitant psychiatric symptoms.

[Emotion and basal ganglia (I): what can we learn from Parkinson's disease?].

PubMed

Dondaine, T; Péron, J

2012-01-01

Parkinson's disease provides a useful model for studying the neural substrates of emotional processing. The striato-thalamo-cortical circuits, like the mesolimbic dopamine system that modulates their function, are thought to be involved in emotional processing. As Parkinson's disease is histopathologically characterized by the selective, progressive and chronic degeneration of the nigrostriatal and mesocorticolimbic dopamine systems, it can therefore serve as a model for assessing the functional role of these circuits in humans. In the present review, after a definition of emotional processing from a multicomponential perspective, a synopsis of the emotional disturbances observed in Parkinson's disease is proposed. Note that the studies on the affective consequences of subthalamic nucleus deep brain stimulation in Parkinson's disease were excluded from this review because the subject of a companion paper in this issue. This review leads to the conclusion that several emotional components would be disrupted in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. We then discuss the functional roles of the striato-thalamo-cortical and mesolimbic circuits, ending with the conclusion that both these pathways are indeed involved in emotional processing. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

MCD spectroscopy and TD-DFT calculations of low symmetry subnaphthalocyanine analogs.

PubMed

Mack, John; Otaki, Tatsuya; Durfee, William S; Kobayashi, Nagao; Stillman, Martin J

2014-07-01

Magnetic circular dichroism (MCD) spectroscopy and time-dependent density functional theory (TD-DFT) calculations are used to analyze the electronic structure and optical properties of low-symmetry subnaphthalocyanine analogs with AAB and ABB structures formed during mixed condensations of tetrafluorophthalonitrile and 2,3-naphthalenedicarbonitrile. The results demonstrate that trends observed in the properties of phthalocyanine analogs can be used to fine tune the optical properties so that the Q(0,0) bands lie in the red region, in a manner that does not significantly destabilize the highest occupied molecular orbital (HOMO) energy relative to that of the parent subphthalocyanine ligand. Attempts to study the spectroscopy of anion radical species proved unsuccessful, since they proved to be unstable. Copyright © 2014 Elsevier Inc. All rights reserved.

Geographic and Ethnic Variation in Parkinson Disease: A Population-Based Study of US Medicare Beneficiaries

PubMed Central

Wright Willis, Allison; Evanoff, Bradley A.; Lian, Min; Criswell, Susan R.; Racette, Brad A.

2010-01-01

Background Parkinson disease is a common neurodegenerative disease. The racial, sex, age, and geographic distributions of Parkinson disease in the US are unknown. Methods We performed a serial cross-sectional study of US Medicare beneficiaries aged 65 and older from the years 1995, and 2000–2005. Using over 450,000 Parkinson disease cases per year, we calculated Parkinson disease prevalence and annual incidence by race, age, sex, and county. Spatial analysis investigated the geographic distribution of Parkinson disease. Results Age-standardized Parkinson disease prevalence (per 100,000) was 2,168.18 (±95.64) in White men, but 1,036.41 (±86.01) in Blacks, and 1,138.56 (±46.47) in Asians. The incidence ratio in Blacks as compared to Whites (0.74; 95% CI = 0.732–0.748) was higher than the prevalence ratio (0.58; 95% CI = 0.575–0.581), whereas the incidence ratio for Asians (0.69; 95% CI = 0.657–0.723) was similar to the prevalence ratio (0.62; 95% CI = 0.617–0.631). Bayesian mapping of Parkinson disease revealed a concentration in the Midwest and Northeast regions. Mean county incidence by quartile ranged from 279 to 3,111, and prevalence from 1,175 to 13,800 (per 100,000). Prevalence and incidence in urban counties were greater than in rural ones (p < 0.01). Cluster analysis supported a nonrandom distribution of both incident and prevalent Parkinson disease cases (p < 0.001). Conclusions Parkinson disease is substantially more common in Whites, and is nonrandomly distributed in the Midwest and Northeastern US. PMID:20090375

Particle identification using digital pulse shape discrimination in a nTD silicon detector with a 1 GHz sampling digitizer

NASA Astrophysics Data System (ADS)

Mahata, K.; Shrivastava, A.; Gore, J. A.; Pandit, S. K.; Parkar, V. V.; Ramachandran, K.; Kumar, A.; Gupta, S.; Patale, P.

2018-06-01

In beam test experiments have been carried out for particle identification using digital pulse shape analysis in a 500 μm thick Neutron Transmutation Doped (nTD) silicon detector with an indigenously developed FPGA based 12 bit resolution, 1 GHz sampling digitizer. The nTD Si detector was used in a low-field injection setup to detect light heavy-ions produced in reactions of ∼ 5 MeV/A 7Li and 12C beams on different targets. Pulse height, rise time and current maximum have been obtained from the digitized charge output of a high bandwidth charge and current sensitive pre-amplifier. Good isotopic separation have been achieved using only the digitized charge output in case of light heavy-ions. The setup can be used for charged particle spectroscopy in nuclear reactions involving light heavy-ions around the Coulomb barrier energies.

Mood changes following social dance sessions in people with Parkinson's disease.

PubMed

Lewis, Carine; Annett, Lucy E; Davenport, Sally; Hall, Amelia A; Lovatt, Peter

2016-04-01

Dance interventions have physical benefits for the elderly, especially those with Parkinson's disease. This study assessed the psychological benefits of dance. A total of 37 participants, with either Parkinson's disease (n= 22) or age-matched controls (n= 15) completed mood questionnaires before and after a 10-week dance intervention. An overall reduction in total mood disturbance and a specific reduction in anger were observed. In addition, less fatigue was found for those initially scoring higher in depression. This suggests that dance can provide psychological benefits for both people with Parkinson's disease and the elderly, with findings suggesting that this is an avenue to be explored further. © The Author(s) 2014.

Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomized placebo-controlled trial

PubMed Central

Lenze, Eric J.; Mulsant, Benoit H.; Blumberger, Daniel M.; Karp, Jordan F.; Newcomer, John W.; Anderson, Stewart J.; Dew, Mary Amanda; Butters, Meryl A.; Stack, Jacqueline A.; Begley, Amy E.; Reynolds, Charles F.

2015-01-01

Summary Background Treatment-resistant major depressive disorder is common and potentially life-threatening in older persons, in whom little is known about the benefits and risks of augmentation pharmacotherapy. Methods We conducted a multi-site, placebo-controlled, randomized clinical trial to test the efficacy and safety of aripiprazole augmentation for older adults with treatment-resistant depression. We treated 468 participants aged 60 and older with current major depressive episode with venlafaxine extended-release (ER); 96 (20.5%) did not complete this open phase, 191 (40.8%) remitted, and 181 (38.7%) did not remit and were randomized to 12 weeks of double-blind augmentation with aripiprazole or placebo. The computer-generated randomization was done in blocks and stratified by site. The primary endpoint was remission, defined as Montgomery-Asberg Depression Rating Scale scores ≤10 (and at least two points below the score at the start of the randomized phase) at both of the final two consecutive visits. We also assessed resolution of suicidal ideation, and safety and tolerability with cardiometabolic and neurological measures. Analyses were conducted according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT00892047. Findings Older adults on aripiprazole had a higher remission rate than those on placebo (44% versus 29%; odds ratio [OR]=2.0, 95% CI 1.1–3.7, p=0.03; number needed to treat [NNT]=6.6 [95% CI 3.5–81.8]). Overall, remission was stable during 12 additional weeks of continuation treatment. The resolution of suicidal ideation was more marked with aripiprazole than with placebo. Akathisia was the most common adverse effect (27% of participants on aripiprazole). Compared to placebo, aripiprazole was also associated with more Parkinsonism but not with treatment-emergent suicidal ideation, QTc prolongation, or increases in adiposity, glucose, insulin, or lipids. Interpretation In older adults who fail

Measuring the Burden of Hospitalization in Patients with Parkinson´s Disease in Spain

PubMed Central