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Sökning: WFRF:(Dizdar Dizdar Segrell Nil)

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1.
  • Ahmadi, Ahmad, et al. (författare)
  • Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
  • 2012
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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2.
  • Davidsson, Anette, et al. (författare)
  • Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinsons disease and Atypical Parkinsonian syndromes using DaTSCAN (R) SPECT
  • 2014
  • Ingår i: Annals of Nuclear Medicine. - : Springer Verlag (Germany). - 0914-7187 .- 1864-6433. ; 28:9, s. 851-859
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To verify if I-123-FP-CIT, DaTSCAN (R) can differentiate early stages of Parkinsons disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinsons disease. Methods 128 consecutive patients were investigated with I-123-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI. Results In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking. Conclusion In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN (R) SPECT in this material.
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3.
  • Diczfalusy, Elin, et al. (författare)
  • A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis
  • 2011
  • Ingår i: Medical and Biological Engineering and Computing. - : Springer Publishing Company. - 0140-0118 .- 1741-0444. ; 49:12, s. 1459-1469
  • Tidskriftsartikel (refereegranskat)abstract
    • Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.
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4.
  • Diczfalusy, Elin, et al. (författare)
  • Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation
  • 2012
  • Ingår i: IEEE Engineering in Medicine and Biology Society (EMBC), 2012. - : IEEE. - 9781424441198 - 9781424441204 - 9781457717871 ; , s. 6438-6441
  • Konferensbidrag (refereegranskat)abstract
    • Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It  was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.
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5.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.
  • 1991
  • Ingår i: Melanoma Research. - 0960-8931. ; 1:1, s. 33-42
  • Tidskriftsartikel (refereegranskat)abstract
    • A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.
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6.
  • Dizdar (Dizdar Segrell), Nil, 1960-, et al. (författare)
  • Analysis of L-dopa in human serum
  • 2002
  • Ingår i: BioTechniques. - 0736-6205 .- 1940-9818. ; 33:5, s. 1000-1002
  • Tidskriftsartikel (refereegranskat)
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7.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice
  • 2000
  • Ingår i: Cancer chemotherapy and pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 45:3, s. 192-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Glutathione is an important cellular compound which affects detoxification of electrophiles and may have direct or indirect effects on pigment formation. It is therefore of importance to study interstitial concentrations in melanoma tissue while decreasing its formation with an enzyme inhibitor and increasing its amount with cysteine deliverers. Method: Glutathione formation was inhibited by intraperitoneal (i.p.) injection of BSO. N-Acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) were then given i.p. to subgroups of the animals. Intratumoral microdialysis was performed during BSO treatment, during BSO treatment combined with NAC or OTC and after discontinuation of BSO but ongoing NAC or OTC treatment. Results: Glutathione formation was inhibited during BSO treatment. The dialysate concentrations of both glutathione and cysteine decreased during concomitant treatment with BSO and NAC or OTC. Recovery of the amounts of the two compounds was seen in both groups after discontinuation of BSO treatment. In the NAC group we also observed an acute increase in dialysate concentrations of cysteine after NAC injection. The 5-S-cysteinyldopa concentrations were unaffected by variations in glutathione and cysteine concentrations. Conclusions: 5-S-Cysteinyldopa in melanoma is not formed from glutathione in vivo to any appreciable extent. The intracellular amount of cysteine is probably not a limiting factor for cysteinyldopa formation. It seems that both NAC and OTC can be used as cysteine deliverers to melanoma cells in vivo to produce recovery of glutathione levels after synthesis inhibition by BSO treatment.
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8.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants
  • 1997
  • Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 7:4, s. 322.-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.
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9.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis
  • 1999
  • Ingår i: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 45:10, s. 1813-1820
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.
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10.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma
  • 1999
  • Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 100:4, s. 231-237
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.
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11.
  • Dizdar (Dizdar Segrell), Nil, et al. (författare)
  • Letter: Untitled
  • 2013
  • Ingår i: Journal of Neuroscience Methods. - : Elsevier. - 0165-0270 .- 1872-678X. ; 212:2, s. 363-363
  • Tidskriftsartikel (refereegranskat)abstract
    • n/a
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12.
  • Dizdar (Dizdar Segrell), Nil (författare)
  • Microdialysis as a Tool in Studies of L-Dopa and Metabolites in Malignant Melanoma and Parkinson’s Disease
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A model with human melanoma xenografts transplanted to athymic mice has been adopted for in vivo studies of 5-S-cysteinyldopa (an intermediate pigment metabolite), glutathione, and cysteine. L-Dopa is an intermediate metabolite in pigment formation and is also important in the treatment of Parkinson's disease, and therefore 1 have also studied the pharmacokinetics of this compound.We were first to describe in vivo microdialysis in melanoma tissue and showed that dialysis membranes of cuprophane or polyamide are suitable for studies of interstitial 5-S-cysteinyldopa and selected thiols. Analytical procedures were also improved for quantitation of 5-S-cysteinyldopa, L-dopa, glutathione, cysteine, and N-acetylcysteine (NAC). In the melanoma xenografts the interstitial concentration of 5-S-cysteinyldopa reflected the high intracellular production of this intermediate metabolite. For in vivo manipulation of glutathione in the melanoma tissue we gave intraperitoneal injection of buthionine sulphoximine to the animals and thus reduced the glutathione concentrations substantially. We showed that restitution of glutathione in melanoma tissue occurs spontaneously and is not much improved by treatment with the cysteine deliverers NAC and L-2-oxothiazolidine-4-carboxylate (OTC). 5-S-Cysteinyldopa was not substantially affected by great variations in glutathione concentrations. Transport of NAC from intraperitoneal injection to melanoma tissue occurred rapidly and deacetylation to cysteine in vivo could be detected soon after NAC injection. In vivo formation of cysteine was slower from OTC than from NAC.Pharmacokinetic studies of L-dopa in human subjects indicated a slight to moderate protein binding. Plasma free L-dopa had similar elimination T½ as interstitial L-dopa, but in some cases the elimination of total L-dopa was slower. Difficulties in intestinal absorption of L-dopa were revealed by microdialysis in blood and subcutaneous tissue. Studies showed that this was due to delayed emptying of the stomach. L-Dopa intake increased 5-S-cysteinyldopa concentrations in blood within 30 min in patients with Parkinson's disease and a history of melanoma. No melanoma activation occurred during long-term treatment with L-dopa.Microdialysis is thus a safe and easily applied method for in vivo studies of both pigment metabolites from human melanoma tissue transplanted to nude mice and for pharmacokinetic studies of L-dopa.
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13.
  • Gati, Istvan, et al. (författare)
  • Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability
  • 2010
  • Ingår i: Neurological Research. - : Forefront Publishing Group. - 0161-6412 .- 1743-1328. ; 32:6, s. 650-655
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to establish three-dimensional cultures originating from muscle biopsies and evaluate the viability and morphology. Method: Muscle biopsies from patients with suspected neuromuscular disorders were obtained and established as primary muscle tissue cultures. Tissue pieces, 1-2 mm of diameters, were placed in culture medium and subjected to sporadic stirring to prevent attachment and outgrowth as monolayer cells. Morphology and ability to attach to the surface were investigated by light microscopy. Viability was evaluated by Tc-99m-tetrofosmin uptake. After 1 month, histology was evaluated by light microscopy and immunocytochemistry. The findings of a healthy muscle and a dystrophic muscle were compared. Results: Initially, the tissue pieces were unshaped but formed spheroid-like structures during the culture period. For dystrophic muscle, attachment capacity to the surface was initially potent and decreased during the culture period, whereas control muscle showed weak attachment from the start that increased during the culture period. The uptake of Tc-99m-tetrofosmin increased in control muscle, while it decreased in dystrophic muscle, during the culture period. The histological investigation demonstrated larger destruction of myofiber, weaker satellite cell activation and reduced myofiber regeneration in the dystrophic muscle as compared to the control muscle. Conclusion: The cellular components of the muscle tissue can survive and proliferate as spheroid-like primary cultures. The cellular composition resembles the in vivo condition, which allows studies of degeneration of the original fibers, and activation and proliferation of the satellite cells. The culture system may provide better understanding of the degeneration and regeneration processes in different muscle disorders and allow investigations of pharmacological interventions.
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14.
  • Georgiopoulos, Charalampos, et al. (författare)
  • DaTSCAN SPECT EVALUATION OF PATIENTS WITH MOVEMENT DISORDERS
  • 2011
  • Ingår i: EUROPEAN JOURNAL OF NEUROLOGY. - : Wiley-Blackwell. ; , s. 567-567
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Molecular imaging with DaTSCAN SPECTis widely used as a diagnostic tool in patients with movementdisorders in the form of Parkinson's Disease (PD),Parkinson-plus syndromes and Tremor. In the present studythe potency of DATScan SPECT to detect degeneration inthe basal ganglia in early stages of PD, before the onset ofmedication, is evaluated. In addition the efficacy ofDaTSCAN for differential diagnosis between patients withidiopathic PD and patients with Parkinson-plus syndromesis examined.Methodology: Participants: 21 patients with PD in earlystages, before the onset of medication, 20 patients withidiopathic PD and 6 patients with Parkinson-plussyndromes. 15 participants with normal results ofDaTSCAN SPECT and a clinical diagnosis different fromPD or Parkinson-plus were used as control.DaTSCAN SPECT: In the present study the quantificationof Striatum Occipital/Occipital and the Xeleris workstation(GE) were used.Results: The quantification for patients with idiopathic PD(1.185±0.05687) was significantly lower (p<0.0001) fromthe control (2.369±0.1258) and significantly lower (p<0.05)from that of patients in early stages of PD, before the onsetof medication (1.359±0.05324). There was no significantdifference between the idiopathic PD and Parkinson-plussyndromes (1.103±0.2442).Conclusion: DaTSCAN SPECT can detect efficiently earlydegeneration in the basal ganglia before the onset ofmedication is needed. Its efficacy for the differentialdiagnosis between idiopathic PD and Parkinson-plussyndromes is questioned. The combination of imaging andclinical examination is mandatory for a certain diagnosis.
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15.
  • Georgiopoulos, Charalampos, et al. (författare)
  • The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes.
  • 2015
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 262:9, s. 2154-2163
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinson's disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand (123)I-FP-CIT (DaTSCAN(®)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.
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16.
  • Kronstrand, Robert, et al. (författare)
  • Quantitative Analysis of Desmethylselegiline, Methamphetamine, and Amphetamine in Hair and Plasma from Parkinson Patients on Long-Term Selegiline Medicatio
  • 2003
  • Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 27:3, s. 135-141
  • Tidskriftsartikel (refereegranskat)abstract
    • Hair and plasma from patients on long-term selegiline medication were analyzed to evaluate the relationships between plasma and hair melanin concentrations and the incorporation of the selegiline metabolites methamphetamine and amphetamine in hair, and to evaluate hair analyses for determining compliance in medication. Analyses were performed on both the whole hairs, as well as pigmented and non-pigmented hairs from gray-haired patients. Melanin was quantitated by spectrophotometry, and metabolites were quantitated by gas chromatography-mass spectrometry. Concentrations in pigmented and non-pigmented hairs differed significantly for both methamphetamine (p < 0.01) and amphetamine (p < 0.02), with mean concentration ratios being 3.69 ± 1.88 and 2.95 ± 1.16 for methamphetamine and amphetamine, respectively. Segmental analysis indicated that some patients had not been compliant with medication. We concluded that the incorporation of methamphetamine and amphetamine into hair of single individuals shows a preference for pigmented hairs over white hairs and that segmental analysis of hair may he useful when measuring compliance with medication.
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17.
  • Lill, Christina M., et al. (författare)
  • The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
  • Tidskriftsartikel (refereegranskat)abstract
    • A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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18.
  • Nord, Maria, et al. (författare)
  • The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
  • 2010
  • Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 25:3, s. 363-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.
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19.
  • Pihlstrom, L., et al. (författare)
  • Fine mapping and resequencing of the PARK16 locus in Parkinson's disease
  • 2015
  • Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 60:7, s. 357-362
  • Tidskriftsartikel (refereegranskat)abstract
    • The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinson's disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5' region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.
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20.
  • Pihlstrom, L., et al. (författare)
  • Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease
  • 2013
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:6
  • Tidskriftsartikel (refereegranskat)abstract
    • enome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
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21.
  • Pohl, Petra, et al. (författare)
  • The Ronnie Gardiner Rhythm and Music Method – a feasibility study in Parkinson’s disease
  • 2013
  • Ingår i: Disability and Rehabilitation. - : Informa Healthcare. - 0963-8288 .- 1464-5165. ; 35:26, s. 2197-2204
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To assess the feasibility of the novel intervention, Ronnie Gardiner Rhythm and Music (RGRM™) Method compared to a control group for patients with Parkinson’s disease (PD).Method: Eighteen patients, mean age 68, participating in a disability study within a neurological rehabilitation centre, were randomly allocated to intervention group (n = 12) or control group (n = 6). Feasibility was assessed by comparing effects of the intervention on clinical outcome measures (primary outcome: mobility as assessed by two-dimensional motion analysis, secondary outcomes: mobility, cognition, quality of life, adherence, adverse events and eligibility). Results: Univariable analyses showed no significant differences between groups following intervention. However, analyses suggested that patients in the intervention group improved more on mobility (p = 0.006), cognition and quality of life than patients in the control group. There were no adverse events and a high level of adherence to therapy was observed. Conclusions: In this disability study, the use of the RGRM™ Method showed promising results in the intervention group and the adherence level was high. Our results suggest that most assessments chosen are eligible to use in a larger randomized controlled study for patients with PD.Implications for RehabilitationThe RGRM™ Method appeared to be a useful and safe method that showed promising results in both motor and cognitive functions as well as quality of life in patients with moderate PD.The RGRM™ Method can be used by physiotherapists, occupational, speech and music therapists in neurological rehabilitation.Most measurements were feasible except for Timed-Up-and-Go.  
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22.
  • Pålhagen, S. E., et al. (författare)
  • Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease
  • 2012
  • Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 126:6, s. e29-e33
  • Tidskriftsartikel (refereegranskat)abstract
    • Background - 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. Methods - Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, andgt;= 3 months after surgery, and then every 3 months. Results - Twenty-seven treatment-naive subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean +/- SD), baseline = 52.1 +/- 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 +/- 16.7, N = 27, P = 0.003; month 12 = 42.5 +/- 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean +/- SD), baseline = 33.6 +/- 10.8, N = 27, month 0 = 27.1 +/- 11.8, N = 27, P = 0.001; 12 months = 28.8 +/- 12.8, n = 23, P = 0.126. Conclusions - LCIG provides functional improvement beginning at first visit that is sustained for 12 months.
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23.
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24.
  • Zsigmond, Peter (författare)
  • Biochemical and pharmacokinetic studies in vivo in Parkinson’s disease
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Parkinson’s disease (PD) is a neurodegenerative disease affecting approximately 25000 people in Sweden. The main cause of the disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) projecting to the striatum. The motor symptoms of PD, due to decreased levels of dopamine, includes bradykinesia, rigidity and tremor.During the 1960ies oral L-dopa treatment was introduced increasing quality of life for PD patients. In recent decades, enzyme inhibitors have been introduced, increasing bioavailability of L-dopa in plasma. After 5-10 years of L-dopa treatment, 50% of PD patients develop disabling dyskinesias. This can be due to rapid changes in L-dopa conentrations with non physiological stimulation of the dopamine receptor.For over 20 years deep brain stimulation (DBS) has grown to be a good neurosurgical procedure for improving quality of life in advanced PD with disabling dyskinesias. With stereotactic technique, electrodes are implanted in the brain and connected to a pacemaker sending electrical impulses. The most common target in PD is the subthalamic nucleus (STN). The knowledge about DBS mechanism(s) and its interaction with L-dopa is unsatisfactory.The aims of this thesis were; to study the effect of the enzyme inhibitor entacapone on the L-dopa concentration over the blood brain barrier (BBB); to study possible interactions between L-dopa and DBS; to study alterations in neurotransmitters during DBS; to visualize microdialysis catheters in anatomical targets and to estimate sampling area of the catheters.In all four papers the microdialysis technique was used. It is a well-established technique for continuous sampling of small water-soluble molecules within the extracellular fluid space in vivo, allowing studies of pharmaceutical drugs and neurotransmitters.We showed that entacapone increases the bioavailability of L-dopa in blood with a subsequent increase of L-dopa peak levels in the cerebrospinal fluid. This in turn may cause a larger burden on the dopaminergic neurons causing an increased degeneration rate and worsening of the dyskinesias; we showed that 18% of L-dopa crosses the BBB and that there is a possible interaction between L-dopa and DBS, L-dopa concentrations increase during concomitant STN DBS, which can clarify why its possible to decrease L-dopa medication after DBS surgery. The research has also shown that STN DBS has an effect on various neurotransmitter systems, mainly L-dopa, dopamine and GABA. We showed that STN DBS may have an effect on the SNc, resulting in putaminal dopamine release.We have shown that with stereotactic technique, it is safe to do microdialysis sampling in specific areas in the human brain. Simulations with the finite element method combined with patient specific preoperative MRI and postoperative CT images gave us exact knowledge about the positions of the catheters and that the studied structures were the intended. The research has given an assumption of the maximum tissue volume that can be sampled around the microdialysis catheters.
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25.
  • Zsigmond, Peter, et al. (författare)
  • Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
  • 2014
  • Ingår i: Neurology and Clinical Neuroscience. - : John Wiley & Sons. - 2049-4173. ; 2:5, s. 149-155
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.
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26.
  • Zsigmond, Peter, et al. (författare)
  • Stereptactic microdialysis of the basal ganglia in Parkinson's disease
  • 2012
  • Ingår i: Journal of Neuroscience Methods. - : Elsevier. - 0165-0270 .- 1872-678X. ; 207:1, s. 17-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious treatment in patients with advanced Parkinson's disease, yet the mechanisms of STN DBS are poorly understood. The aims of this study were to develop a useful method for studying neurotransmitter alterations during DBS and for the pharmacokinetics of L-dopa in brain tissue. Ten patients with Parkinson's disease participated, whereof two had no previous L-dopa medication. The electrodes and catheters were placed using MRI-guided stereotaxic targeting. Two microdialysis probes were placed, one in the right internal globus pallidus, and one in a brachial vein. The quadripolar deep brain electrodes were placed in the right STN. Microdialysates from brain tissue and blood were collected in 15-min fractions at baseline and during DBS. After stimulation new baseline fractions were taken and finally three fractions during continuous intravenous infusion of L-dopa. Clinical evaluation showed that both DBS and L-dopa infusion gave good relief of rigidity and tremor in all ten patients. During DBS the L-dopa levels in the brain increased in some of the patients but did not persist during the whole stimulation period. The concentration in brain increased substantially during intravenous L-dopa infusion. A number of catecholamines and their metabolites were analysed with high pressure liquid chromatography (HPLC). With our study we could show that this model is suitable for the monitoring of neurotransmitters and for pharmacokinetic studies in human brain, although we found that the sampling time was too short to follow the possible alterations in brain activity caused by DBS.
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27.
  • Bergquist, Filip, et al. (författare)
  • Parkinsons sjukdom [Parkinsons disease] : heterogen och komplex i sitt kliniska uttryck [heterogeneous and complex in its clinical presentation]
  • 2020
  • Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • Parkinsons disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinsons disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinsons disease.
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28.
  • Bergquist, Filip, et al. (författare)
  • Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
  • 2022
  • Ingår i: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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29.
  • Cedergren Weber, Gustav, et al. (författare)
  • The Impact of COVID-19 on Parkinson's Disease : A Case-Controlled Registry and Questionnaire Study on Clinical Markers and Patients' Perceptions
  • 2023
  • Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 2023
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Parkinson's disease (PD) is a neurodegenerative disease with motor and nonmotor symptoms. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Objectives: To explore how COVID-19 affects motor, nonmotor, and general health aspects of PD and to map how PD patients perceive their change in symptoms since falling ill with COVID-19.Method: The study was descriptive, case-controlled, and based on both registry and questionnaire data. At baseline, the controls were matched on age, sex, and disease severity. Information on the severity of the disease, nonmotor symptoms, motor symptoms, and general health was retrieved from the Swedish Registry for PD. Registry data from a COVID-19 group (n=45) and a control group (n=73), as well as questionnaires from a COVID-19 group (n=24) and a control group (n=42), were compared.Results: We did not find that SARS-CoV-2 infection affects any major aspect of nonmotor symptoms, motor symptoms, general health, and perception of change in PD patients' post-COVID-19. Compared to controls, the COVID-19 group reported a more positive subjective experience of pain and quality of life and a perception of change post-COVID-19 regarding general motor function, sleep quality, and mood (all p<0.05).Conclusion: Although SARS-CoV-2 infection does not seem to affect PD symptoms in any major respect, the subjective experience of several aspects of life in PD patients might be slightly improved post-COVID-19 compared to a control group. The findings warrant further investigations due to the small sample size and possible survivorship bias.
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30.
  • Davidsson, Anette, et al. (författare)
  • Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinson's disease and Atypical Parkinsonian snydromes using DaTSCAN SPECT
  • 2014
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Parkinson's disease (PD) is a degenerative disorder characterized by the progressive degeneration of dopamine-containing cells in substantia nigra, and it is the second most common neurodegenerative disorder worldwide. It can be difficult to differentiate between idiopathic PD and Atypical Parkinsonian syndromes (APS). In a high percentage of APS patients, the right diagnosis is not established even during late stages of the disease. Currently there is no specific test to verify PD, especially in the early stages of the disease.The aim was to verify if 123I-FP-CIT, DaTSCAN ® can differentiate early stages of Parkinson's disease as well as patients with Atypical Parkinsonian syndromes from manifest Parkinson's disease.Materials and methods: 121 consecutive patients were investigated with 123I-FP-CIT SPECT, during a four year period. All patients were diagnosed according to the established consensus criteria for diagnosis of Parkinson's disease (PD), (n=53), Atypical Parkinsonian syndromes (APS) (n=18). Remaining patients were grouped early PD (before onset the of L-dopa medication), (n=20), and non-PD syndromes (n=30). SPECT images were analysed visually according to a predefined ranking scale of dopaminergic degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) to a more global and severe degeneration pattern (burst striatum). Striatum ratios were quantitatively analysed with the 3D software, EXINI.Results: In the group of APS patients the burst striatum pattern was most frequent and found in 61% (11/18 patients). In PD patients the egg shape pattern was dominating, especially in early PD where it was present in 95% (19/20 patients). The sensitivity of burst striatum degeneration pattern was 61% (95%-CI 36-83%), specificity 90% (95%-CI 81-96%). The sensitivity of egg shape pattern was 74% (95%-CI 62-84%), specificity 90% (95%-CI 47-90%). The uptake ratios were reduced in both PD and APS patients and closely related to the image pattern. The lowest putamen/caudate ratio was found in early PD.Conclusion: In this study we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios, but combining visual assessment with uptake ratios did not add to the discriminating power of DATSCAN ® SPECT in this materialReferences: Kahraman D, Eggers C, Schicha H, Timmermann L, Schmidt M. Visual assessment of dopaminergic degeneration pattern in 123I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease. J Neurol. 2012;259:251-60
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31.
  • Eek, Tom, et al. (författare)
  • Odor Recognition Memory in Parkinson's Disease : A Systematic Review
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
  • Forskningsöversikt (refereegranskat)abstract
    • Olfactory impairment is a central non-motor symptom in Parkinson's disease (PD). Previous studies have demonstrated that olfactory dysfunction is associated with mental illness and impaired cognition. The frequently investigated olfactory functions are odor detection, discrimination, and identification. However, few studies have focused on odor recognition memory (ORM). ORM tasks involves episodic memory which therefore can facilitate the detection of dementia among patients with PD and consequently adjust their treatment. Thus, the aim of this systematic review is to summarize the existing research on ORM in PD. Databases and reference lists were used for data collection. Studies were included in the review if they met the eligibility criteria derived from the PICOS-framework. Quality evaluation of the studies was based on the STROBE-statement. Six studies with small samples were included in the analysis which demonstrated the scarce research on the subject. The studies targeting ORM were heterogenous and involved two main tasks: odor recognition and odor matching. The synthesis of the data demonstrated that PD patients performed significantly lower than controls on both tasks, especially on odor matching task. Only the odor recognition task exhibited a difference between patients with PD vs. Alzheimer's disease (AD). PD patients performed significantly better than AD patients. The findings based on the available limited data support the notion that odor recognition task can be of importance in identifying Parkinson's disease dementia (PDD). To investigate this hypothesis, future research needs to include larger samples of PD, PDD and AD patients executing the same odor recognition task.
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32.
  • Fardell, Camilla, et al. (författare)
  • S100B polymorphisms are associated with age of onset of Parkinson's disease
  • 2018
  • Ingår i: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 19:42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In this study we investigated the association between SNPs in the S100B gene and Parkinson's disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3'-UTR of the S100B gene, was strongly associated with age of onset of PD.
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33.
  • Gati, Istvan, 1954-, et al. (författare)
  • Effects of inhibitors of the arachidonic acid cascade on primary muscle culture from a Duchenne muscular dystrophy patient
  • 2007
  • Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 77:3-4, s. 217-223
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to elucidate the mechanisms of action for potential targets of therapeutic intervention related to the arachidonic acid cascade in muscular dystrophy. Primary cultures from a Duchenne patient were used to study the expression of dystrophin-1, utrophin, desmin, neonatal myosin heavy chain (MHCn) and Bcl-2 during inhibition of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX). Hypo-osmotic treatment was applied in order to trigger Ca2+ influx and PLA2 activity. Inhibition of PLA2 and LOX with prednisolone and nordihydroguaiaretic acid (NDGA) caused a semi-quantitative increase of utrophin and Bcl-2-, and a dose-dependent, quantitative increase of desmin expression, an effect that was augmented by hypo-osmotic treatment. Our results indicate that LOX inhibitors, similarly to corticosteroids, can be beneficial in the treatment of muscular dystrophies. © 2007 Elsevier Ltd. All rights reserved.
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34.
  • Georgiopoulos, Charalampos, et al. (författare)
  • A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease
  • 2019
  • Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.
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35.
  • Georgiopoulos, Charalampos, et al. (författare)
  • Olfactory fMRI: Implications of Stimulation Length and Repetition Time
  • 2018
  • Ingår i: Chemical Senses. - : OXFORD UNIV PRESS. - 0379-864X .- 1464-3553. ; 43:6, s. 389-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.
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36.
  • Georgiopoulos, Charalampos, et al. (författare)
  • Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.
  • 2017
  • Ingår i: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7:2, s. 301-311
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.
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37.
  • Hellqvist, Carina, et al. (författare)
  • Improving self-management for persons with Parkinson's disease through education focusing on management of daily life : patients' and relatives' experience of the Swedish National Parkinson School.
  • 2018
  • Ingår i: Journal of Clinical Nursing. - : Wiley-Blackwell Publishing Ltd. - 0962-1067 .- 1365-2702. ; 27:19-20, s. 3719-3728
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS AND OBJECTIVE: The two folded aim of this study was firstly to identify and describe experiences valuable for managing daily life after participation in the NPS self-management intervention. The second part was to explore the applicability of the Self- and family management framework by Grey and colleagues for persons with Parkinson's Disease and their relatives. BACKGROUND: The impact of PD is evident on the lives of both patients and relatives. The National Parkinson School (NPS) is a Swedish self-management program designed for patients and relatives, aiming at teaching strategies helpful for the ability of self-management, in order to promote life satisfaction. DESIGN: Qualitative explorative with inductive and deductive analysis. METHODS: Five group discussions with NPS participants were audio-recorded. Verbatim transcriptions were analysed inductively with thematic analysis according to Braun and Clarke, and the findings were then applied deductively to the existing model for patients with chronic disease. RESULTS: Through the first step of inductive analysis three themes capturing the meaning, value and experience of being a participant at the NPS were identified: Exchanging experiences and feeling support, Adjustment and acceptance of PD for managing daily life, and Promoting life satisfaction. The deductive analysis applied the inductive findings to the Self-and family management framework of chronically ill to explore the fit to persons with PD and relatives attending the NPS program. CONCLUSIONS: The NPS program is a promising approach for helping persons with PD and their relatives to achieve better self-management of disease and improved life satisfaction. Further evaluations of program outcomes in clinical practice are warranted. RELEVANCE OF CLINICAL PRACTICE: Self-management programs like the NPS is a promising approach in facilitating a positive mind-set and outlook on life and gain knowledge to understand, adapt and handle chronic disease, such as PD, better. This article is protectedby copyright. All rights reserved.
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38.
  • Hellqvist, Carina, 1976-, et al. (författare)
  • Self-management education for persons with Parkinson's disease and their care partners : a quasi-experimental case-control study in clinical practice
  • 2020
  • Ingår i: Parkinson's Disease. - : Hindawi Limited. - 2090-8083 .- 2042-0080. ; 2020, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Parkinson's disease is a neurodegenerative condition with both physical and mental consequences that affect many aspects of everyday life. Persons with Parkinson's disease and their care partners want guidance from healthcare services in order to develop skills to adjust to life with a long-term condition. The Swedish National Parkinson School is a dyadic self-management programme to support both persons with Parkinson's disease and care partners. Objective To assess the outcomes of the Swedish National Parkinson School as reported by participants. Design A quasi-experimental case-control study in clinical care using self-reported questionnaires. Participants Swedish National Parkinson School was offered by health care professionals working in clinical care. Participants in the programme were also asked to participate in the study. A matched control group was recruited for a comparison of findings. In total, 92 persons with Parkinson's disease and 55 care partners were included. Settings. Five Swedish geriatric and neurologic outpatient clinics. Method Data were collected during 2015-2017, before and after participation in the National Parkinson School or before and after seven weeks of standard care. Outcomes were assessed using generic and Parkinson's specific questionnaires. Descriptive statistics were used to describe baseline characteristics. Mann-Whitney U and Chi(2) tests were used to test for between-group differences and within-group differences were tested by the Wilcoxon signed-ranks test. Results Improvements regarding health status, constructive attitudes and approaches, and skill and technique acquisition were found after the intervention among persons with Parkinson's disease. No changes were found among care partners. Conclusion The findings indicate that the Swedish National Parkinson School may improve health status and self-management among persons with Parkinson's disease, but further studies are needed to better understand the effects of the programme.
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39.
  • Hellqvist, Carina, 1976- (författare)
  • Self-management support to handle everyday life with Parkinson´s disease
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Being diagnosed with Parkinson´s disease (PD) is a life-altering experience. The long-term condition requires continuous adjustments to the everyday life not only of the person affected, but also for care partners. There is still insufficient knowledge on how best to support this process of acceptance and adjustment to encourage self-management.Aims: The aim of this thesis is to enhance the knowledge and understanding of self-management for persons with PD (PwPD) and their care partners. Furthermore, to investigate whether the self-management intervention Swedish National Parkinson School can be used as a tool to support self-management, and how nurses specialised in the care of persons with Parkinson´s disease can tailor their support to encourage self-management in everyday life. Method and design: Both qualitative and quantitative designs and methods were used in the three studies included in this thesis. Participants included a total of 209 persons. Of these, 127 were persons with PD and 75 were care partners. Participants with PD were largely in the middle stages of the disease. The time since diagnosis ranged from less than one year to over 20 years, and most participants had lived with the disease for around five years. Participants were cared for at five separate outpatient clinics, both geriatric and neurological, in three county and two university hospitals across Sweden. Data collection included observations, interviews, self-reported questionnaires and audio-recordings of the National Parkinson School in clinical care. The overall results of this thesis were obtained using a qualitative approach, where the results of the three studies were analysed using qualitative thematic analysis as described by Braun and Clarke (2006).Results: In combining the results of the separate studies through thematic analysis three distinct but interrelated themes were evident. These described the processes and efforts of persons to accept, manage and adjust to everyday life with PD. The theme “A changed reality” involves participants´ descriptions of how life changed after the diagnosis of PD. For many this was a shock, and both the person affected and their care partners experienced a variety of emotions such as anger, denial and hopelessness. It changed their personal identities, their perception of themselves as individuals and as a couple. They worried about what the future would hold, and the uncertainty was hard to accept and handle. One strategy for processing and beginning to acknowledge the new situation involved speaking openly about the diagnosis. The second theme “Finding a new path”, involves a description of how, after accepting or at least acknowledging, their new reality, participants started to find ways of managing the impact of PD on everyday life, incorporating it into their current life and identity. Many felt new knowledge was needed and turned to books and websites on PD. An intervention which was appreciated in terms of providing tools for self-observation and self-knowledge was the Swedish National Parkinson School. Participants later used these techniques to communicate and observe symptoms and healthcare needs. Being an active participant in life and performing activities such as physical exercise or other activities they enjoyed were also used as a strategy to feel satisfaction in life. Participants frequently worked out self-care and compensatory strategies to handle everyday tasks. Another strategy they found comforting and helpful involved retaining a positive mind-set and believing that a good future lay ahead. In the third category “The companions”, the participants described self-management in everyday life as a task they performed together. Management of PD was considered the shared responsibility of the person affected and the care partner, but was also influenced by others such as family members and close friends. The Swedish National Parkinson School provided knowledge as a form of common ground for the person affected and the care partner. During the Swedish National Parkinson School, the social interaction involved in exchanging experiences and feeling support from others in the same situation was considered helpful and was much appreciated.Conclusions: Management of PD in everyday life involves both the person affected and the care partner. After the initial emotional reactions, alongside feelings of lost identity and an altered life, persons started to look to the future and were ready to find ways of handling the changed conditions of their everyday lives. Persons with PD and their care partners were now willing to learn more about PD and to find tools and strategies to help them manage its impact on their everyday lives. During this phase, they appreciated the support of the Swedish National Parkinson School intervention. In the intervention, they would meet others in the same situation to find support and exchange experiences. They also turn to healthcare for support in the process of self-management in everyday life. Nurses working specifically to support PwPD and their CP will need to tailor support taking into account the disease trajectory as well as the psychological processes involved in accepting and adjusting to PD to best fit the unique needs and wishes of every person with PD and their care partner.
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40.
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41.
  • Nord, Maria, et al. (författare)
  • Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
  • 2017
  • Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing. - 2169-9712 .- 2169-9720. ; 06:01
  • Tidskriftsartikel (refereegranskat)abstract
    • Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.
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42.
  • Nord, Maria, et al. (författare)
  • Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
  • 2017
  • Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing Inc. - 2169-9712 .- 2169-9720. ; 6:2, s. 52-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
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43.
  • Nyholm, Dag, et al. (författare)
  • Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations.
  • 2009
  • Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 119:5, s. 345-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.
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44.
  • Nyholm, D, et al. (författare)
  • Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease
  • 2005
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 64:2, s. 216-223
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). Methods: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/ carbidopa gel for 3 + 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from -3 to 0 to +3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. Results: Median percentage of ratings in a functional "on" interval (-1 to +1) was increased from 81 to 100% by infusion therapy (p < 0.01). This improvement was accompanied by a decrease in "off" state (p < 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p < 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p < 0.01). Adverse events were similar for both treatment strategies. Conclusions: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.
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45.
  • Petzold, Axel, et al. (författare)
  • Longitudinal one-year study of levels and stoichiometry of neurofilament heavy and light chain concentrations in CSF in patients with multiple system atrophy.
  • 2009
  • Ingår i: Journal of the neurological sciences. - : Elsevier BV. - 1878-5883 .- 0022-510X. ; 279:1-2, s. 76-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Two cerebrospinal fluid (CSF) biomarkers specific for neurodegeneration have recently emerged - the neurofilament light (NfL, 68 kDa) and heavy (NfH, 190-210 kDa) chains. This study investigated whether the CSF NfH and NfL levels or their stoichiometric relationship changed over time in a neuroprotective treatment trial. METHODS: Serial CSF samples (n=95) from 42 patients with multiple system atrophy (MSA), half randomized to treatment with recombinant human growth hormone (r-hGH) and the other half to placebo, were collected at baseline, 6 and 12 months. The concentration of CSF NfL and NfH was determined using standard ELISAs. RESULTS: There was no consistent change in the levels of either protein over the 12 month period, or between treatment with active r-hGH versus placebo. The molar stoichiometry of CSF NfL:NfH was 4:1 (R=0.37, p=0.0002) and increased following treatment with r-hGH (p=0.03). CONCLUSION: These results indicate that CSF levels of both NfL and NfH on their own are not useful markers of disease progression in MSA, at least over a 12-month period. Future work is needed to elucidate whether the CSF stoichiometry and dynamics of Nf subunits in individual patients are a feature of the underlying pathology and of diagnostic or prognostic value.
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46.
  • Pohl, Petra, et al. (författare)
  • Group-based music intervention in Parkinsons disease : findings from a mixed-methods study
  • 2020
  • Ingår i: Clinical Rehabilitation. - : Sage Publications. - 0269-2155 .- 1477-0873. ; 34:4, s. 533-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate a group-based music intervention in patients with Parkinsons disease. Design: Parallel group randomized controlled trial with qualitative triangulation. Setting: Neurorehabilitation in primary care. Subjects: Forty-six patients with Parkinsons disease were randomized into intervention group (n = 26), which received training with the music-based intervention, and control group (n = 20) without training. Interventions: The intervention was delivered twice weekly for 12 weeks. Main measures: Primary outcome was Timed-Up-and-Go subtracting serial 7s (dual-task ability). Secondary outcomes were cognition, balance, concerns about falling, freezing of gait, and quality of life. All outcomes were evaluated at baseline, post-intervention, and three months post-intervention. Focus groups and individual interviews were conducted with the intervention group and with the delivering physiotherapists. Results: No between-group differences were observed for dual-task ability. Between-group differences were observed for Falls Efficacy Scale (mean difference (MD) = 6.5 points; 95% confidence interval (CI) = 3.0 to 10.0, P = 0.001) and for Parkinson Disease Questionnaire-39 items (MD = 8.3; 95% CI = 2.7 to 13.8, P = 0.005) when compared to the control group post-intervention, but these were not maintained at three months post-intervention. Three themes were derived from the interviews: Expectations versus Results, Perspectives on Treatment Contents, and Key Factors for Success. Conclusion: Patient-reported outcomes and interviews suggest that the group-based music intervention adds value to mood, alertness, and quality of life in patients with Parkinsons disease. The study does not support the efficacy in producing immediate or lasting gains in dual-tasking, cognition, balance, or freezing of gait.
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47.
  • Pålhagen, Sven E., et al. (författare)
  • Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinsons disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs
  • 2016
  • Ingår i: Parkinsonism & Related Disorders. - : ELSEVIER SCI LTD. - 1353-8020 .- 1873-5126. ; 29, s. 17-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinsons disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. Methods: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naive (N = 37), or had previous LCIG treatment for amp;lt;2 (N = 22), or amp;gt;= 2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinsons Disease Rating Scale (UPDRS), 39-item Parkinsons Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. Results: Mean monthly costs per patient ( 8226 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naive patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. Conclusions: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naive patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The longterm safety was consistent with the established LCIG profile. (C) 2016 AbbVie Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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48.
  • Svenningsson, P., et al. (författare)
  • A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia
  • 2020
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:6, s. 1046-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • Background IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 mu M on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. (c) 2020 International Parkinson and Movement Disorder Society
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49.
  • Vigren, Patrick, et al. (författare)
  • Awake craniotomy in epilepsy surgery includes previously inoperable patients with preserved efficiency and safety
  • 2023
  • Ingår i: International Journal of Neuroscience. - : TAYLOR & FRANCIS LTD. - 0020-7454 .- 1563-5279.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Whilst awake craniotomy has been widely used historically in epilepsy surgery, the safety and efficacy of this approach in epilepsy surgery has been sparsely investigated in controlled studies. The objective of this study is to investigate the safety and efficacy of awake resection in epilepsy surgery and focuses on the possibility to widen surgical indications with awake surgery. Methods: Fifteen patients operated with awake epilepsy surgery were compared to 30 matched controls undergoing conventional/asleep epilepsy surgery. The groups were compared with regard to neurological complications, seizure control and location of resection. Results: Regarding seizure control, 86% of patients in the awake group reached Engel grade 1-2 compared to 73% in the control group, operated with conventional/asleep surgery, not a statistically significant difference. Neither was there a statistical significant difference regarding postoperative neurological complications. However, there was a significant difference in location of the resection when comparing the two groups. Of the 15 patients operated with awake intraoperative mapping, four had previously been considered as non-operable by epilepsy surgery centres, due to vicinity to eloquent brain regions and predicted risk of post-operative neurological deficits. Discussion: The results show that awake epilepsy surgery yields similar level of seizure control when compared to conventional asleep surgery, with maintained safety in regard to neurological complications. Furthermore, the results indicate that awake craniotomy in epilepsy surgery is feasible and possible in patients otherwise regarded as inoperable with epileptigenic zone in proximity to eloquent brain structures.
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50.
  • Willows, Thomas, et al. (författare)
  • Initiation of Levodopa-Carbidopa Intestinal Gel Infusion Using Telemedicine (Video Communication System) Facilitates Efficient and Well-Accepted Home Titration in Patients with Advanced Parkinson's Disease
  • 2017
  • Ingår i: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7:4, s. 719-728
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Levodopa-carbidopa intestinal gel (LCIG; Duodopa r) is used for continuous infusion in advanced Parkinson's disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Objective: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Methods: Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Results: Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours: minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). Conclusions: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses.
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