Anders Johansson

Enteral Levodopa/Carbidopa infusion in advanced Parkinson disease : Long-term exposure

Objectives: In patients with advanced Parkinson disease, levodopa/carbidopa formulated as a gel suspension (Duodopa) permits continuous delivery into the small intestine using a portable pump, resulting in less variability in levodopa concentrations and fewer motor fluctuations and dyskinesias than with oral levodopa administration. This is a retrospective analysis of the long-term clinical experience with this agent. Methods: All but 1 of the patients who had received enteral levodopa infusion treatment between January 1, 1991, and June 30, 2002, consented to a review of their hospital charts. Results Of the 65 patients with initial testing of the treatment, 86% opted for continued treatment via percutaneous endoscopic gastrostomy or gastrojejunostomy. Total exposure to levodopa infusion was 216 patient-years (mean, 3.7 years). Maximum treatment duration was 10.7 years. Fifty-two patients were treated for 1 year or longer. The adverse effect profile of levodopa/carbidopa infusion was similar to that observed with oral administration of levodopa. Seven deaths occurred, all considered unrelated to the treatment. Intestinal tube problems, including dislocation of the intestinal tube to the stomach, were the most common technical problem, occurring in 69% of the patients during the first year. The optimal daily dose of levodopa decreased by an average of 5% during follow-up. Conclusions: The safety of enteral infusion of levodopa/carbidopa formulated as a gel suspension was found acceptable. For most patients, the technical challenges posed by the enteral infusion system were offset by the improvement in motor fluctuations and dyskinesias offered by this technique.

Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease

Background:  Infusion of levodopa/carbidopa intestinal gel (Duodopa®; Abbott) was introduced in Sweden in 1991 as an experimental treatment in advanced Parkinson’s disease and obtained EU approval in 2004. There is compelling evidence for short‐term use of this treatment; however, long‐term data are scarce.

Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease

This interim 12‐month analysis is a part of an open‐label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health‐related quality of life (HRQoL) effects in routine care.

Levodopa infusion combined with entacapone or tolcapone in Parkinson disease : a pilot trial

Background and purpose:  Catechol‐O‐methyltransferase inhibitors may be used to decrease levodopa requirement. The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol‐O‐methyltransferase inhibitors are added.

Deposition of palladium nanoparticles on the pore walls of anodic alumina using sequential electroless deposition

Palladium nanoparticles were deposited using a sequential electroless deposition technique on the pore walls of nanoporous anodic alumina. For the particle deposition a Pd(NH3)42+ solution was soaked in the alumina membrane and a heated air flow was applied in order to reduce the palladium complex to palladium metal nanoparticles. By repeating the deposition process the size of the nanoparticles could be tailored in this investigation between 6 and 11nm. The size of the nanoparticles was also affected by the concentration of the Pd(NH3)42+ solution, i.e., higher concentration yielded larger particle mean diameters. The samples were investigated using high resolution scanning electron microscopy, x-ray diffraction (XRD), inductively coupled plasma with a mass spectrometer, high resolution transmission electron microscopy, and energy dispersive spectroscopy (EDS). Analysis revealed narrow size distributions of the particles as well as uniform particle coverage of the pore walls. No by-products were observed...

Well-ordered nanopore arrays in rutile TiO2 single crystals by swift heavy ion-beam lithography

Ion track lithography has been applied for transferring the self-ordered nanopattern of porous anodic alumina to single-crystalline rutile TiO2 substrates. As a result, nanometre resolved arrays have been fabricated with an aspect ratio ranging from 5 to 16, over areas of several square millimetres. Differences in the expected aspect ratio of the resulting nanopores in rutile TiO2 single crystals are analysed and discussed. Some of these differences may be ascribed to varying densities of the mask material.

Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease.

ObjectiveThe aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion. MethodsA nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in “on” state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes. ResultsIndividual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias. ConclusionsMotor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.

A first principles derivation of animal group size distributions

Several empirical studies have shown that the animal group size distribution of many species can be well fit by power laws with exponential truncation. A striking empirical result due to Niwa is that the exponent in these power laws is one and the truncation is determined by the average group size experienced by an individual. This distribution is known as the logarithmic distribution. In this paper we provide first principles derivation of the logarithmic distribution and other truncated power laws using a site-based merge and split framework. In particular, we investigate two such models. Firstly, we look at a model in which groups merge whenever they meet but split with a constant probability per time step. This generates a distribution similar, but not identical to the logarithmic distribution. Secondly, we propose a model, based on preferential attachment, that produces the logarithmic distribution exactly. Our derivation helps explain why logarithmic distributions are so widely observed in nature. The derivation also allows us to link splitting and joining behavior to the exponent and truncation parameters in power laws.

Current-reinforced random walks for constructing transport networks

Biological systems that build transport networks, such as trail-laying ants and the slime mould Physarum, can be described in terms of reinforced random walks. In a reinforced random walk, the route taken by ‘walking’ particles depends on the previous routes of other particles. Here, we present a novel form of random walk in which the flow of particles provides this reinforcement. Starting from an analogy between electrical networks and random walks, we show how to include current reinforcement. We demonstrate that current-reinforcement results in particles converging on the optimal solution of shortest path transport problems, and avoids the self-reinforcing loops seen in standard density-based reinforcement models. We further develop a variant of the model that is biologically realistic, in the sense that the particles can be identified as ants and their measured density corresponds to those observed in maze-solving experiments on Argentine ants. For network formation, we identify the importance of nonlinear current reinforcement in producing networks that optimize both network maintenance and travel times. Other than ant trail formation, these random walks are also closely related to other biological systems, such as blood vessels and neuronal networks, which involve the transport of materials or information. We argue that current reinforcement is likely to be a common mechanism in a range of systems where network construction is observed.

Fabrication of high-density ordered nanoarrays in silicon dioxide by MeV ion track lithography

Self-assembled nanoporous alumina films were employed as masks for MeV ion track lithography. Films with thickness of 2 μm and pore diameters of 30 and 70 nm were attached to thermally grown SiO2 covered with a thin gold layer. The samples were aligned with respect to the beam by detecting backscattered He+ ions with the initial energy of 2 MeV. The ordered pattern of the porous alumina films was successfully transferred into SiO2 after irradiation with a 4 MeV Cl2+ beam at fluence of 1014ions∕cm2, followed by chemical etching in a 5% HF solution.