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

Untersuchung eines möglichen neuroprotektiven Effektes der Kainsäure- und Chinolinsäureläsion des Nucleus subthalamicus auf dopaminerge Neurone der Substantia nigra im 6-Hydroxydopamin- und im 3-Nitropropionsäure-Parkinson-Tiermodell der Ratte.

Das idiopathische Parkinson-Syndrom zählt zu den häufigsten neuro¬logischen Erkrankungen. Der ihm zugrundeliegende progressive Verlust dopaminerger nigrostriataler Neurone in der Pars compacta der Substantia nigra und das daraus resultierende Dopamindefizit innerhalb des Striatums führt nach der heutigen Kenntnis der Organi¬sation der Basalganglien zu einer enthemmten Aktivität des Ncl. Subthalamicus und nachfolgend zur Hyperaktivität inhibitorischer GABAerger Neuronen des medialen Pallidumsegments auf Thalamus¬kerngebiete. Somit sinkt die exzitatorische Funktion der Thalamus¬kern¬gebiete auf die motorischen Kortexareale. Neuerdings werden exzitatorische glutamaterge Neurone zwischen dem Ncl. Subthalamicus und der Substantia nigra postuliert, wobei unter Umständen die neurotoxische Eigenschaft des Glutamats auf metabolisch vorgeschädigte dopaminerge Neurone der Substantia nigra bei der Äthiologie des Morbus Parkinson eine Rolle spielen könnte. Schon seit einiger Zeit kommt klinisch die funktionelle Ausschaltung des Ncl. Subthalamicus oder des medialen Pallidumsegments mittels chronischer Hochfrequenzstimulation bzw. die thermokoagulatorische Läsion des medialen Pallidumsegments beim fortgeschrittenen Morbus Parkinson zum Einsatz. Der genaue Wirkmechanismus der oben angeführten Eingriffe ist noch nicht hinreichend geklärt. In der vorliegenden Arbeit wurde der neuroprotektive Effekt von Kainsäure- und Chinolinsäureläsionen des Ncl. Subthalamicus auf dopaminerge Neurone der Pars compacta der Substantia nigra im subakuten 6-Hydroxydopamin- und im 3-Nitropropionsäure-Modell des Morbus Parkinson untersucht. Hierbei konnten die Ergebnisse anderer Arbeitsgruppen nicht gestützt werden, wonach eine Läsion des Ncl. Subthalamicus neuroprotektive Effekte auf die Neuronenpopulationen der Substantia nigra zeigen soll. Eine Wiederholung der Experimente mit größerer Fallzahl erscheint zwingend notwendig, dies insbesondere, weil sich aus den Ergeb¬nissen der Arbeiten entscheidende klinisch-therapeutische Konse¬quenzen mit Folgen für die Prognose der Erkrankten ergeben könnten

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)

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

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

TEM study of the martensitic phases in the ductile DyCu and YCu intermetallic compounds

DyCu and YCu are representatives of the family of CsCI-type B2 rare earth intermetallic compounds that exhibit high room temperature ductility. Structure, orientation relationship, and morphology of the martensites in the equiatomic compounds DyCu and YCu are examined using transmission electron microscopy (TEM). TEM studies show that the martensite structures in DyCu and YCu alloys are virtually identical. The martensite is of orthorhombic CrB-type B33 structure with lattice parameters a = 0.38 nm, b = 1.22 nm, and c = 0.40 nm. (02 (1) over bar) twins were observed in the B33 DyCu and YCu martensites. The orientation relationship of B33 and B2 phases is (11 (1) over bar)[112]B33 parallel to (110)[001]B2. The simulated electron diffraction patterns of the B33 phase are consistent with those of experimental observations. TEM investigations also reveal that a dominant orthorhombic FeB-type B27 martensite with lattice parameters a = 0.71 nm, b = 0.45 nm, and c = 0.54 nm exists in YCu alloy. (I (1) over barI) twins were observed in the B27 YCu martensite. The formation mechanism of B2 to B33 and B2 to B27 phase transformation is discussed

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