Parkinson's Disease: Clinical Signs and Symptoms, Neural Mechanisms, Positron Emission Tomography, and Therapeutic Interventions

Parkinson's disease is one of the most frequent neurodegenerative brain diseases. Its time course is slow and is characterized by progressive loss of dopaminergic and other brainstem neurons resulting in malfunctioning of the cerebral neuronal systems responsible for motor functions. The clinical signs are slowness of movement, muscle rigidity and rest-tremor amongst other features. The cause of the disease is unknown, but recently involvement of genetic factors is being researched. Positron emission tomography (PET) allows in vivo determination of striatai dopaminergic activity. This has increased our insight in the pathophysiology of the disease and permits direct study of disease progression at a biochemical level and equally to monitor whether potential neuroprotective interventions are indeed effective. Thus far no drug has emerged but promising substances are currently being studied

Finite surgeries on three-tangle pretzel knots

We classify Dehn surgeries on (p,q,r) pretzel knots that result in a manifold of finite fundamental group. The only hyperbolic pretzel knots that admit non-trivial finite surgeries are (-2,3,7) and (-2,3,9). Agol and Lackenby's 6-theorem reduces the argument to knots with small indices p,q,r. We treat these using the Culler-Shalen norm of the SL(2,C)-character variety. In particular, we introduce new techniques for demonstrating that boundary slopes are detected by the character variety.Comment: 18 pages, 15 figures v2 - minor revisions throughou

Literatur-Rundschau

Beck, Hanno: Medienökonomie - Print, Fernsehen und Multimedia (Steffen W. Hillebrecht)Mendack, Susanne: Berufsfeld Journalismus (=fit for business 513) (Steffen W. Hillebrecht) Müller-Thurau, Claus-Peter: Berufsfeld Zeitungsverlag(= fit for business) (Steffen W. Hillebrecht) Verband der Zeitschriftenverlage in Bayern (Hg.): Zeitschriften im Unterricht. Medienkundliches Handbuch (Ferdinand Oertel)Wirtz, Bernd B.: Medien- und Internet-Management (Steffen W. Hillebrecht) Zoche, Hermann-Josef/unter Mitarbeit von Bernhard Meuser: Die Jesus-AG. Ein Unternehmensberater analysiert die älteste Firma der Welt (Steffen W. Hillebrecht)

Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients.

BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the "wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (P<O.01 v placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (P<0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (P<0.05), "on" time increased by 21.3% (P<0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (P<0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy

The economic benefit of timely, adequate, and adherence to Parkinson's disease treatment: the Value of Treatment Project 2

Background: Parkinson's disease (PD) is a chronic progressive neurological disorder with a high psychosocial and economic burden. As part of the European Brain Council (EBC)-led Value of Treatment project, this study aimed to capture the economic benefit of timely, adequate, and adherence to PD treatment. Methods: The EBC Value of Treatment Initiative combined different stakeholders to identify unmet needs in the patients’ journey according to Rotterdam methodology. The economic evaluation focused on three major topics identified as major gaps: start of treatment; best treatment for advanced disease; and adherence to treatment. Two separate healthcare systems (Germany and the UK) were chosen. Cost-effectiveness was determined by using decision-analytical modelling approaches. Effectiveness was expressed as quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER). Results: Treatment intervention in PD was found to be cost-effective regardless of the initial health state of the patient receiving the treatment. Cost savings were between -€1000 and −€5400 with 0.10 QALY gain and -€1800 and -€7600 with 0.10 QALY gain for Germany and the UK, respectively. Treatment remains cost-effective within the National Institute for Health and Care Excellence thresholds. Availability of adequate treatment to more patients was also found to be cost-effective, with an ICER of €15,000–€32,600 across country settings. Achieving the target adherence to treatment would generate cost-savings of €239,000–€576,000 (Germany) and €917,000–€2,980.000 (UK) for every 1,000 patients treated adequately. Conclusions: The analyses confirmed that timely, adequate, and adherence to PD treatment will not only improve care of the patients but is also cost-effective across healthcare systems. Further studies with a distinct identification of gaps in care are necessary to develop better and affordable care

Particle dynamics of a cartoon dune

The spatio-temporal evolution of a downsized model for a desert dune is observed experimentally in a narrow water flow channel. A particle tracking method reveals that the migration speed of the model dune is one order of magnitude smaller than that of individual grains. In particular, the erosion rate consists of comparable contributions from creeping (low energy) and saltating (high energy) particles. The saltation flow rate is slightly larger, whereas the number of saltating particles is one order of magnitude lower than that of the creeping ones. The velocity field of the saltating particles is comparable to the velocity field of the driving fluid. It can be observed that the spatial profile of the shear stress reaches its maximum value upstream of the crest, while its minimum lies at the downstream foot of the dune. The particle tracking method reveals that the deposition of entrained particles occurs primarily in the region between these two extrema of the shear stress. Moreover, it is demonstrated that the initial triangular heap evolves to a steady state with constant mass, shape, velocity, and packing fraction after one turnover time has elapsed. Within that time the mean distance between particles initially in contact reaches a value of approximately one quarter of the dune basis length

Meson loop effects in the NJL model at zero and non-zero temperature

We compare two different possibilities to include meson-loop corrections in the Nambu-Jona-Lasinio model: a strict 1/N_c-expansion in next-to-leading order and a non-perturbative scheme corresponding to a one-meson-loop approximation to the effective action. Both schemes are consistent with chiral symmetry, in particular with the Goldstone theorem and the Gell-Mann-Oakes-Renner relation. The numerical part at zero temperature focuses on the pion and the rho-meson sector. For the latter the meson-loop-corrections are crucial in order to include the dominant rho -> pipi-decay channel, while the standard Hartree + RPA approximation only contains unphysical qqbar-decay channels. We find that m_\pi, f_\pi, and quantities related to the rho-meson self-energy can be described reasonably with one parameter set in the 1/N_c-expansion scheme, whereas we did not succeed to obtain such a fit in the non-perturbative scheme. We also investigate the temperature dependence of the quark condensate. Here we find consistency with chiral perturbation theory to lowest order. Similarities and differences of both schemes are discussed.Comment: 51 pages, 18 figures, to be published in Physics of Atomic Nuclei, the volume dedicated to the 90th birthday of A.B. Migdal, error in Eq. 4.22 correcte