Classification of advanced stages of Parkinson's disease: translation into stratified treatments.

Advanced stages of Parkinson's disease (advPD) still impose a challenge in terms of classification and related stage-adapted treatment recommendations. Previous concepts that define advPD by certain milestones of motor disability apparently fall short in addressing the increasingly recognized complexity of motor and non-motor symptoms and do not allow to account for the clinical heterogeneity that require more personalized approaches. Therefore, deep phenotyping approaches are required to characterize the broad-scaled, continuous and multidimensional spectrum of disease-related motor and non-motor symptoms and their progression under real-life conditions.

Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines.

Carrageenan (CGN) is a common food additive used for its gelling and thickening properties. The present study was done to evaluate intestinal permeability, cytotoxicity, and CGN-mediated induction of proinflammatory cytokines. A standard Caco-2 absorption model showed no CGN permeability or cytotoxicity at concentrations of 100, 500, and 1000 μg/mL.

Laboratory assessments in the course of Parkinson's disease: a clinician's perspective.

Physicians, caregivers and patients themselves must be alert to the onset of and changes in motor and non-motor features during the course of Parkinson's disease (PD). Parallel laboratory routine assessments are necessary because of the evolving impairment of the general health status of the individual. A number of potential biomarkers for the diagnosis of PD are currently under investigation, with diagnosis early in the disease course a particular goal, even before the onset of motor symptoms.

Thrombolysis in a stroke patient on dabigatran anticoagulation: case report and synopsis of published cases.

We present the case of an aphasic 77-year-old stroke patient with left distal M1 occlusion who received rt-PA for thrombolysis while on oral anticoagulant treatment with dabigatran (150 mg b.i.d.

Diurnal variation of hypothalamic function and chronic subthalamic nucleus stimulation in Parkinson's disease.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinson's disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients.

[Early deep brain stimulation for Parkinson's disease].

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment for advanced Parkinson's disease with levodopa-induced motor complications. Randomized controlled studies have shown that motor fluctuations and quality of life are significantly more improved by STN-DBS than by best medical treatment. The main delay before neurosurgery is currently 14 years after diagnosis.

The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil.

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil.

Scales in Parkinson's disease.

The search for valid instruments to measure different domains of health disturbances becomes increasingly important for the assessment of Parkinson's disease. The most widely used tool is the Unified Parkinson's Disease Rating Scale (UPDRS) which was introduced in 1987 and is currently awaiting revision. In addition, a variety of instruments have been used to capture non-motor aspects of Parkinson's disease but only a minority of these instruments has been validated for this particular disease condition.

Drug costs for patients with Parkinson's disease in two different European countries.

Objective: To examine factors that influence drug costs in patients with Parkinson's disease (PD) and to compare the costs in two different countries.

Methods: We examined drug costs among 438 patients with PD (286 from Germany and 152 from Norway) and collected information on the patients' age, medication, disease duration, and Hoehn & Yahr stage.

Results: Drug expenses rose with increasing severity and duration of the disease.

Structure and markers of appropriateness, quality and performance of drug treatment over a 1-year period after hospital discharge in a cohort of elderly patients with cardiovascular diseases from Germany.

In a group of elderly patients over 65 years of age with at least two cardiovascular diagnoses requiring chronic medication (n=424), drug therapy at hospital discharge and at home thereafter was followed for a 1-year period. Two home visits took place at 3 months and 12 months after initial discharge. A median of six prescriptions had already been given at the time of discharge; this number increased slightly during ambulatory follow-up.

Which factors influence therapeutic decisions in Parkinson's disease?

Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years, some but not all pathogenetic mechanisms causing dyskinesias in PD have become better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors.

Efficacy of cabergoline in long-term use: results of three observational studies in 1,500 patients with Parkinson's disease.

The tetracyclic ergoline derivative cabergoline was investigated in three studies to test its efficacy in treating the motor symptoms of Parkinson's disease. In two studies, it was used as an add-on agent to the previous medication regimen that included other parkinsonian drugs, including levodopa. In the third study, cabergoline was switched from another dopamine agonist.

Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron emission tomography in patients with Parkinson's disease.

Objective: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6-fluorine 18, an established imaging method for striatal dopaminergic neurons.

Methods: Twenty-three patients in different disease stages (Hoehm and Yahr stage 2.

Pharmacokinetic-pharmacodynamic relationship of levodopa with and without tolcapone in patients with Parkinson's disease.

Objective: To investigate the effect of administration of the catechol-Omethyltransferase (COMT) inhibitor tolcapone on the concentration-effect relationship of levodopa in patients with advanced Parkinson's disease and on-off fluctuations.

Design: Nonblind single-group 2-period pharmacokinetic-pharmacodynamic study.

Patients And Participants: 12 patients, mean age 59 years, with idiopathic Parkinson's disease and response fluctuations.

Workshop III: late motor complications of Parkinson's disease.

The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can delay the onset of late motor complications and reduce their severity. L-Dopa remains the most potent anti-parkinsonian medication, but its use for the initial therapy of Parkinson's disease is limited to elderly patients.

Dyskinesia in Parkinson's disease. Pathophysiology and clinical risk factors.

Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years some but not all pathogenetic mechanisms causing dyskinesias in PD have been better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors.

The effect of exercise on pharmacokinetics and pharmacodynamics of levodopa.

The aim of our study was to evaluate the influence of low-intensity exercise on levodopa absorption and levodopa motor effect. We studied the pharmacokinetics and pharmacodynamics of levodopa under resting conditions and under a workload of 50 watts for 2 hours on a cycle ergometer in 12 parkinsonian patients with predictable fluctuations of motor disability. The patients attended the hospital on both days in a provoked off state.

Therapeutic value of exercise training in Parkinson's disease.

Purpose: The objective of this study was to investigate the influence of an intensive exercise training on motor disability, mood, and subjective well-being in parkinsonian patients.

Methods: The study was designed as an open long-term pilot trial over 20 wk. Sixteen slightly to moderately affected idiopathic parkinsonian patients (PD) were included.

Exercise test in Parkinson's disease.

Unlabelled: In this study we assessed cardiovascular performance and metabolic response after an exercise test in Parkinsonian patients (PD patients).

Methods: 15 PD patients (10 male, 5 female; mean age:63 +/- 6.17 y; mean weight: 72.

Concentration-response relationship of levodopa in patients at different stages of Parkinson's disease.

Objective: To assess differences in the pharmacokinetic and pharmacodynamic relations of levodopa in clinically defined groups and to prove that pharmacokinetic and pharmacodynamic parameters are associated with duration of disease and length of treatment.

Methods: We studied the pharmacokinetic and pharmacodynamic relations of levodopa after a single dose (100 mg levodopa with 25 mg benserazide) among four groups of patients with Parkinson's disease. Group 1 was levodopa-naive patients (n = 8); group 2 was patients in stable condition taking levodopa (n = 10); group 3 was patients with on-and-off fluctuations (n = 11); and group 4 was patients with on-and-off fluctuations and peak-dose dyskinesia (n = 8).

Dose response and concentration response relationship of apomorphine in patients with Parkinson's disease and end-of-dose akinesia.

The motor response and the PK-PD relationship of the dopamine agonist, apomorphine, after ascending single doses (0.5, 1, 2, 4 mg s.c.

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.

Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian patients with end-of-dose motor fluctuations.

The modification of the pharmacodynamic response to a single oral dose of levodopa/benserazide by the coadministration of the dopamine agonist apomorphine was investigated in parkinsonian patients with end-of-dose motor fluctuations. The relation between levodopa plasma concentrations and motor response was examined in a double-blind, randomized, crossover design in 10 patients with idiopathic Parkinson's disease with end-of-dose motor fluctuations. Oral single-dose challenges with 100 mg of levodopa/25 mg of benserazide were carried out twice in each patient, under coadministration with apomorphine (1 mg/h) or 0.