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  • 1.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Amyotrofisk lateralscleros2007Inngår i: Hjärnan, Karolinska Institutet University Press, Stockhoolm , 2007Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 2.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Neurologi.
    Neurologi i utveckling2004Inngår i: Incitament, s. 5-Artikkel, forskningsoversikt (Annet (populærvitenskap, debatt, mm))
  • 3.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Ny utgåva av neuroanatomisk klassiker: Per Brodal: The central nervous system2005Inngår i: Läkartidningen, s. 505-Artikkel, omtale (Annet (populærvitenskap, debatt, mm))
  • 4.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Om att breda sin smörgås2006Inngår i: Läkartidningen, Vol. 103, nr 11, s. 830-Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 5.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Parkinson's disease: Swedish pioneering research on pathophysiology and treatment2012Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, nr S1, s. 841-841Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Rörelsestörningar2006Inngår i: Neurologi, Liber AB Stockholm , 2006, s. 568-Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 7.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Boman, Gunnar
    Institutionen för medicinska vetenskaper.
    Nyholm, Dag
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Från Alzheimer till övervikt2007Bok (Annet (populærvitenskap, debatt, mm))
  • 8.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Fagius, Jan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Den neurologiska undersökningen2006Inngår i: Neurologi, Liber AB Stockholm , 2006, s. 568-Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 9.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Lees, Andrew
    Managing advanced Parkinson's disease: the role of continuous dopaminergic stimulation2007Bok (Annet vitenskapelig)
  • 10.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Development of new levodopa treatment strategies in Parkinson’s disease – from bedside to bench to bedside2017Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 2, s. 71-77Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This review will illustrate the process of moving from an idea through preclinical research and Galenic developments into clinical investigations and finally to approval by regulatory agencies within the European Union. The two new treatment strategies described, levodopa/carbidopa intestinal gel and levodopa/carbidopa microtablets, for advanced Parkinson's disease, have been developed in collaborative research within departments at Uppsala University. With this historical approach, reference priority is given to reports considered to be of special importance for this more than two decades long process from bedside to bench to bedside'.

  • 11.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Neurologi.
    Widner, Håkan
    Utveckling inom motorikområdet2004Inngår i: Incitament, s. 7-9Artikkel, forskningsoversikt (Annet (populærvitenskap, debatt, mm))
  • 12.
    Bredenberg, Susanne
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Nyström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    An automatic dose dispenser for microtablets: A new concept for individual dosage of drugs in tablet form2003Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, Vol. 261, nr 1-2, s. 137-146Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson’s disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.

  • 13.
    Ekegren, Titti
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Hanrieder, Jörg
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Focused proteomics in post-mortem human spinal cord2006Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, nr 9, s. 2364-2371Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    With a highly sensitive electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in minimal amounts of spinal cord from patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from control subjects. The results show 18 versus 16 significantly identified ( p < 0.05) proteins, respectively, all known to be found in the central nervous system. The most abundant protein in both groups was the glial fibrillary acidic protein, GFAP. Other proteins were, for example, hemoglobin alpha- and, chain, myelin basic protein, thioredoxin, R enolase, and cholin acetyltransferase. This study also includes the technique of laser microdissection in combination with pressure catapulting (LMPC) for the dissection of samples and specific neurons. Furthermore, complementary experiments with nanoLC-matrix assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the ESI-FTICR MS screening and provided additional results of further identified proteins.

  • 14.
    Fagius, Jan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Neurologi2006Bok (Annet (populærvitenskap, debatt, mm))
  • 15.
    Fagius, Jan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Neurologisk symtomlära2006Inngår i: Neurologi, Liber AB , 2006, s. 568-Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 16.
    Grundström, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lindeberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Nygren, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Ebendal, Ted
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis1999Inngår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 162, nr 2, s. 169-173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle biopsies from five patients with amyotrophic lateral sclerosis (ALS), six patients with other neuromuscular diseases and eight healthy control persons. All five patients with ALS had higher GDNF mRNA expressions in their biopsies than the healthy control group (almost a three fold increase). Among the other patients only one, who had a rapidly progressing toxic polyneuropathy, showed a GDNF mRNA expression above those of the controls. The BDNF mRNA expressions in the biopsies from the ALS patients were in the same range as those from the healthy controls, although the mean value of the ALS patients was higher. The only biopsy that showed a markedly higher BDNF mRNA expression was taken from one patient with progressive muscular atrophy. These results suggest that increased GDNF mRNA expression in muscle is an unspecific response to ongoing denervation and that this response is maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves to be a constant finding in ALS the rationale for the use of GDNF as a therapeutic agent in ALS must be questioned.

  • 17.
    Hårdemark, Hans-Göran
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Persson, Lennart
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurokir.
    Fagius, Jan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Ingen grund för kritiken2005Inngår i: Läkartidningen, Vol. 102, s. 2885-Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 18.
    Ingelsson, Martin
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Nilsson, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Basun, Hans
    Aquilonius, Sten-Magnus
    Institutionen för neurovetenskap. neurologi.
    Lannfelt, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Konformationsförändrade proteiner orsakar neurodegenerativa sjukdomar2005Inngår i: Läkartidningen, Vol. 102, nr 47, s. 3542-3551Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 19.
    Johansson, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Engler, Henry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Blomquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Scott, Berit
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Evidence for astrocytosis in ALS demonstrated by 11C(L)-deprenyl-D2 PET2007Inngår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 255, nr 1-2, s. 17-22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To use deuterium-substituted [11C](l)-deprenyl PET to depict astrocytosis in vivo in patients with amyotrophic lateral sclerosis (ALS). Background: In human brain, the enzyme MAO-B is primarily located in astrocytes. l-deprenyl binds to MAO-B and autoradiography with 3H-l-deprenyl has been used to map astrocytosis in vitro. Motor neuron loss in ALS is accompanied by astrocytosis and astrocytes may play an active role in the neurodegenerative process. Deuterium-substituted [11C](l)-deprenyl PET provides an opportunity to localize astrocytosis in vivo in the brain of patients with ALS. Methods: Deuterium-substituted [11C](l)-deprenyl PET was performed in seven patients with ALS and seven healthy control subjects. Results: Increased uptake rate of [11C](l)-deprenyl was demonstrated in ALS in pons and white matter. Conclusion: This study provides evidence that astrocytosis may be detected in vivo in ALS by the use of deuterium-substituted [11C](l)-deprenyl PET though further studies are needed to determine whether deuterium-substituted [11C](l)-deprenyl binding tracks disease progression and reflects astrocytosis.

  • 20.
    Nilsson, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Fasth, Karl Johan
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Tedroff, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Hartvig, Per
    Långström, Bengt
    Absorption of L-DOPA from the proximal small intestine studied in the rhesus monkey by positron emission tomography1999Inngår i: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 7, nr 3, s. 185-189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Positron emission tomography (PET) seems to be a valuable method for the understanding of intestinal absorption mechanisms, for simultaneous quantitation of absorption rate and distribution kinetics to the tissues of interest after oral drug delivery. PET was evaluated in three Rhesus monkeys for quantitation of the absorption rate from the gastrointestinal tract and the distribution kinetics into different organs. To obtain optimal standardized conditions for the measurement of absorption the drug was administered via a naso-duodenal catheter directly to the absorption site in the proximal small intestine. l-DOPA was used as study drug given in a suspension together with carbidopa and the radiomarker l-[beta-11C]DOPA. The l-DOPA suspension was given into the duodenum without and after administration of a suspension of six l-amino acids (120 mM) in order to investigate any interaction on the intestinal absorption and distribution of l-DOPA into the liver and brain tissue. Intestinal absorption was in general minor during the first study period and higher together with administered l-amino acids. The somewhat contradictory result with increased absorption when amino acids were present in the intestinal lumen, may be a consequence of increased intestinal motility initiated by the nutrient load.

  • 21.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Neurologi.
    Levodopa infusion therapy in Parkinson Disease2004Inngår i: Clinical Neuropharmacology, Vol. 27, nr 5, s. 245-256Artikkel i tidsskrift (Fagfellevurdert)
  • 22.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Gomes-Trolin, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Knutson, Tina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Nyström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets2003Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 26, nr 3, s. 156-163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.

  • 23.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Ehrnebo, M
    Lewander, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Trolin, C G
    Bäckström, T
    Panagiotidis, G
    Spira, J
    Nyström, C
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 2, s. 124-132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).

    MATERIALS AND METHODS:

    A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.

    RESULTS:

    Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.

    CONCLUSIONS:

    Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.

  • 24.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Johansson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Hellquist, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Complexity of Motor Response to Different Doses of Duodenal Levodopa Infusion in Parkinson Disease2012Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 35, nr 1, s. 6-14Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion.

    METHODS:

    A 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.

    RESULTS:

    Individual 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.

    CONCLUSIONS:

    Motor 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.

  • 25.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kowalski, Jan
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson's disease2004Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 19, nr 4, s. 446-451Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abstract

    Frequent assessment of the symptoms in Parkinson's disease (PD) is important in both clinical and experimental settings, especially when motor fluctuations are present. Patient diaries are increasingly used in studies, allowing patients to stay in their home environments. However, traditional paper diaries may not reflect reality because of a lack in compliance or retrospective data entries. This study presents a comparison between paper diaries and a new method, real-time data capture with a hand-held computer (electronic diary). Twenty patients with PD diagnosed at least 5 years previously were randomly assigned to use either a paper diary or an electronic diary on 8 days during 1 month. Questions were answered every 2 hours over a 12-hour period on each day. Median compliance was 88% with the electronic diary and 98% with the paper diary, although strict compliance to the scheduled times by patients using the paper diary was 78%. Neither age nor earlier experience with computers affected the patient's ability to use the electronic diary. Electronic diaries can be used for self-assessment of PD symptoms. The real-time feature provides fast access to clean data with knowledge of true compliance.

  • 26.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Gomes-Trolin, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Levodopa pharmacokinetics and motor performance during activities of daily living in patients with Parkinson's disease on individual drug combinations2002Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 25, nr 2, s. 89-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pharmacokinetics and pharmacodynamics of levodopa were evaluated at a high-resolution level in a heterogeneous group of 10 patients with idiopathic Parkinson's disease during their normal daily activity. A physician and a nurse spent 10 hours with each patient from the first morning dose of levodopa during daily activities at home and at work. Plasma samples were obtained every 20 minutes for analysis of levodopa and 3-O-methyldopa by high-performance liquid chromatography. To assess clinical response, mobility was rated on every test occasion by patients and by investigators. Food and fluid intake and physical activity were also monitored. There was a large intra- and interindividual variability in the pharmacokinetics of levodopa regardless of the different drug combinations used. Mean plasma levodopa concentration ranged between 0.45 to 7.07 µg/mL and peak concentrations between 0.95 to 13.75 µg/mL. In 44 of 58 dosing events, an oral dose of levodopa was related to a peak in plasma concentration. Assessment of the clinical effects was more sensitive when given by patients than when given by the investigators. The fluctuations of the levodopa concentration in plasma had a clear effect on the clinical parameters assessed, even during early disease stages. Variation in levodopa concentration is the determining factor for motor fluctuations also in patients on clinically optimized combinations with dopamine agonists and enzyme inhibitors.

  • 27.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Johansson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Estrada, Matias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Circadian rhythmicity in levodopa pharmacokinetics in patients with Parkinson disease2010Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 33, nr 4, s. 181-185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:: The purpose of this study was to compare daytime and nighttime plasma pharmacokinetics (PK) of levodopa in patients with Parkinson disease. METHODS:: Four-hour plasma profiles of levodopa were captured in 8 patients with Parkinson disease after the second daily levodopa dose and after the identical dose at bedtime. Patients were fasting 2 hours before and 2 hours after dose intakes, except standardized amounts of tap water. Body position was upright during daytime testing and supine during nighttime testing. Four patients were additionally tested at daytime in supine position. RESULTS:: The absorption rate was significantly delayed at nighttime dosing. The time at which the maximum peaks occurred was delayed from 25 (15-240) to 105 (20-240) minutes, respectively. Maximum concentrations were significantly lower at night, but the plasma exposure (area under the curve, 0-4 hours) was unaffected. Supine daytime plasma PK was in between day and night results. CONCLUSIONS:: There is a slower absorption rate of levodopa during nighttime, probably related to delayed gastric emptying. However, the extent of absorption and bioavailability were unaffected. As the effect of posture on plasma PK was less than the effect of nighttime, this study suggests that the circadian rhythm has a pronounced effect on gastric emptying and absorption rate. Nevertheless, body position may also be an important factor, and it can be recommended that levodopa tablets be taken in upright position that probably should be sustained for at least 30 minutes.

  • 28.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lewander, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Gomes-Trolin, Cecilia
    Bäckström, Tobias
    Panagiotidis, Georgios
    Ehrnebo, Mats
    Nyström, Christer
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers2012Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 35, nr 3, s. 111-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration.

    METHODS: A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.

    RESULTS: The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence.

    CONCLUSIONS: The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.

  • 29.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lewander, Tommy
    Johansson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    LeWitt, Peter A.
    Lundqvist, Christofer
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Enteral Levodopa/Carbidopa infusion in advanced Parkinson disease: Long-term exposure2008Inngår i: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 31, nr 2, s. 63-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 30.
    Nyholm, Dag
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Nilsson Remahl, AIM
    Dizdar, N
    Constantinescu, R
    Holmberg, B
    Jansson, R
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Askmark, Håkan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. neurologi.
    Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease2005Inngår i: Neurology, Vol. 64, s. 216-223Artikkel i tidsskrift (Fagfellevurdert)
  • 31.
    Ramström, Margareta
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik. Analytisk kemi.
    Ivonin, Igor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik. Jonfysik.
    Johansson, Anders
    Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Askmark, Håkan
    Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Zubarev, Roman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik. Jonfysik.
    Håkansson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik. Jonfysik.
    Aquilonius, Sten-Magnus
    Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen. Institutionen för fysikalisk och analytisk kemi, Analytisk kemi. Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik. Analytisk kemi.
    Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry2004Inngår i: Proteomics, nr 4, s. 4010-4018Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study demonstrates the power of a novel proteomic approach developed for the detection and identification of biological markers in body fluids. The goal was to observe alterations in the protein patterns of cerebrospinal fluid (CSF) related to amyotrophic lateral sclerosis (ALS), a neuro-degenerative disorder with unknown etiology. In the experiments, tryptic digests of CSF from patients and healthy controls were analyzed by on-line capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Typically, around 4000 peptides were detected in one such experiment, and a pattern recognition program was constructed for the data analysis to distinguish mass chromatograms from patients and controls. This strategy was evaluated comparing the peptide patterns of CSF spiked in vitro with a biomarker, with control CSF. The patterns were clearly separated and the tryptic peptides of the biomarker were successfully selected as characteristic peaks. Hence, the method was applied to compare mass chromatograms of CSF from 12 ALS-patients and 10 matched healthy controls. While no biomarker alone could be identified from the characteristic peaks, we were able to assign 4 out of 5 unknown samples correctly (i.e. 80% correctly diagnosed, 20% false-negative), and it would be 100% if we reject a possible outlier believed to be caused by an occlusion in the spinal CSF compartment. These findings are very promising, although the clinical relevance is not fully established due to the low number of unknown samples analyzed. In addition to the diagnostic potential, these results may be important steps towards understanding the neurodegenerative process.

  • 32.
    Scott, Berit
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Borgman, Anders
    Johnels, Bo
    Aquilonius, Sten-Magnus
    Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Gender Differences in Parkinson´s disease symptom profile2000Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, Vol. 102, s. 37-43Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Senek, Marina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Bergquist, Filip
    Constantinescu, Radu
    Ericsson, Anders
    Lycke, Sara
    Medvedev, Alexander
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för systemteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Reglerteknik.
    Memedi, Mevludin
    Ohlsson, Fredrik
    Spira, Jack
    Westin, Jerker
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Levodopa/carbidopa microtablets in Parkinson’s disease: A study of pharmacokinetics and blinded motor assessment2017Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, nr 5, s. 563-571Artikkel i tidsskrift (Fagfellevurdert)
  • 34. Sikk, K.
    et al.
    Haldre, S.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Asser, A.
    Paris, M.
    Roose, A.
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, S. -L
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Taba, P.
    Manganese-induced parkinsonism in methcathinone abusers: bio-markers of exposure and follow-up2013Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 20, nr 6, s. 915-920Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. Methods During 20062012 we studied 38 methcathinone abusers with a mean age of 33years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 970 (20 +/- 15)months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. Results The average total UPDRS score was 43 +/- 21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 +/- 3.8ppm) than controls (0.82 +/- 1.02ppm), P=0.02. Plasma Mn concentrations were higher (11.5 +/- 6.2ppb) in active than in former users (5.6 +/- 1.8ppb), P=0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. Conclusion Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.

  • 35. Sikk, K.
    et al.
    Haldre, S.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Petterson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Eriksson, S. -L
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Tonnov, A.
    Taba, P.
    Manganese-induced parkinsonism in methcathinone abusers: biomarkers of exposure and follow-up2012Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, s. 667-667Artikkel i tidsskrift (Annet vitenskapelig)
  • 36. Sikk, Katrin
    et al.
    Taba, Pille
    Haldre, Sulev
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Zjablov, G.
    Asser, T.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Irreversible motor impairment in young addicts - ephedrone, manganism or both?2007Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 115, nr 6, s. 385-389Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background -  Parkinsonian syndrome related to intravenous use of a `designer' psychostimulant, derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in Estonia. Objective -  To describe the symptomatology of four young patients, history of drug administration and chemical analysis of a drug batch. Methods -  Mental and motor function and quality of life were scored and ephedrone was analyzed using electrospray mass spectrometry. Manganese content of the final synthetic mixture was analyzed using Inductively Coupled Plasma-Atomic Emission Spectrometry. Results -  None of the four cases scored below the dementia threshold in MMSE, while other ratings (UPDRS, H&Y, PDQ-39) corresponded to disabilities seen in relatively advanced Parkinson's disease. The ephedrone yield of the reaction was approximately 44% and the mixture was found to contain 0.6 g/l of manganese. Conclusions -  The cases were exposed to extreme manganese load. Their symptomatology is probably identical to manganism. The role of ephedrone is presently unknown. Physicians must be aware of early signs of manganism in patients within social risk groups.

  • 37.
    Vahlquist, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Hällgren, Roger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Alm, Albert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Betungande regler för klinisk forskning står inte i proportion till patientnyttan2005Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, nr 23, s. 1832-1834Artikkel i tidsskrift (Fagfellevurdert)
  • 38.
    Vahlquist, Anders
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Westermark, Per
    Institutionen för genetik och patologi.
    Ståhle, Elisabeth
    Venge, Per
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Påhlmarn, Lars
    Institutionen för kirurgiska vetenskaper.
    Hällgren, Roger
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wiklund, Lars
    Institutionen för kirurgiska vetenskaper.
    Aquilonius, Sten-Magnus
    Institutionen för neurovetenskap. Neurologi.
    Alm, Albert
    Institutionen för neurovetenskap.
    Betungande regler för klinisk prövning står inte i proportion till patientnyttan2005Inngår i: Läkartidningen, Vol. 102, nr 23, s. 1832-1834Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 39.
    Zetterberg, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Lindmark, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Impact of dystonia on quality of life and health in a Swedish population2009Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, nr 6, s. 376-382Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives –  Dystonia is often disabling and disfiguring. The aim of the study was to identify factors influencing the impact of dystonia on self-reported quality of life and health.

    Material and methods –  Members of the Swedish Dystonia Patient Association participated in a survey covering demographic variables, satisfaction with treatment, physiotherapy and physical activity. Quality of life and health were assessed by the Craniocervical Dystonia Questionnaire and the Cervical Dystonia Impact Profile, respectively. Of 378 questionnaires, 76% were analysed. Multiple linear regression analyses were performed to evaluate associations of the above variables with quality of life and health.

    Results –  Level of physical activity and satisfaction with treatment showed the highest association with quality of life and health. No significant relationship was found between form of dystonia and quality of life.

    Conclusions –  The study indicates a need for health care professionals to encourage physical activity and to question dystonia patients about satisfaction with treatment. Further investigations with prospective controlled trials are necessary to evaluate the value of physiotherapy and physical activity in patients with dystonia.

  • 40.
    Zetterberg, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Sjukgymnastik.
    Halvorsen, Kjartan
    Färnstrand, Catarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Aquilonius, Sten-Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lindmark, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Sjukgymnastik.
    Physiotherapy in Cervical Dystonia: Six experimental single-case studies2008Inngår i: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 24, nr 4, s. 275-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the study was to explore the outcome of a physiotherapy program targeted to improve the quality of life of people with cervical dystonia (CD) by reducing pain, improving awareness of postural orientation, increasing muscle strength, and reducing the effort of moving the head and neck. In six single case studies, the primary outcome measure for each case was the Cervical Dystonia Questionnaire (CDQ) to measure the impact of the program on the individuals' quality of life. Secondary outcome measures were identified for the different components of the physiotherapy program: Visual Analogue Scale (pain); Postural Orientation Index (postural orientation awareness); and Movement Energy Index (effort of moving head and neck). Each of the cases had the severity of their problems scored on the Toronto Western Spasmodic Torticollis Scale. The study period was 26 weeks: 2 weeks' baseline period, 4 weeks' treatment period, and 20 weeks' follow-up. All measures except the Movement Energy Index (MEI) and CDQ-24 were taken three times per week for the first 6 weeks of the study and then once at 3 and 6 months. The MEI was taken once a week during the pretreatment and the treatment periods and during the first 2 weeks of follow-up and also after 3 and 6 months of follow-up. The CDQ-24 was taken once in the pretreatment period, once after completion of treatment, once 2 weeks after treatment, and once at 3 and 6 months of follow-up. Five of the six case studies reported an increase in quality of life at 6-month follow-up, as measured on the CDQ-24. Three of the six cases reported a reduction in pain and severity of the dystonia and had improved scores on the postural orientation measure at 6-month follow-up. All six patients had a reduction in the movement energy scores, but this was not significant. The outcomes of the six case studies would suggest that further investigation is required to show the effectiveness of physiotherapy programs in the management of CD.

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