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Sökning: WFRF:(Odin P)

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  • [1]234567Nästa
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1.
  • 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. - : John Wiley and Sons. - 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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2.
  • Hagell, Peter, et al. (författare)
  • Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
  • 1999
  • Ingår i: Brain. - : Oxford University Press. - 1460-2156 .- 0006-8950. ; 122:6, s. 1121-1132
  • Tidskriftsartikel (refereegranskat)abstract
    • Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.
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3.
  • Timpka, Jonathan, et al. (författare)
  • Workforce unavailability in Parkinson's disease
  • 2017
  • Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 135:3, s. 332-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Individuals with Parkinson's disease (PD) become unavailable in the workforce earlier than comparable members of the general population. This may result in significant social insurance expenses, but as workforce participation can be a source for social interaction and a vital part of the personal identity, there are likely to be personal implications extending far beyond the economic aspects. This study aimed to identify aspects that may contribute to workforce unavailability in people with PD. Materials & methods: This was a cross-sectional registry study using data from the Swedish national quality registry for PD and included persons with PD in Skåne County, Sweden who were younger than 65 years. Variables were selected from the registry based on earlier studies and clinical experience and were tested for association with unavailability in the workforce: first in a series of simple regression analyses and then in a multiple logistic regression analysis. Results: A total of 99 persons with PD-of whom 59 were available and 40 were unavailable in the workforce-were included in the study. Age (OR per year: 1.47, 95% CI: 1.18-1.85; P <0.01) and anxiety (OR: 6.81, 95% CI: 1.20-38.67; P = 0.03) were significant contributing factors for unavailability in the workforce. Conclusions: Based on the findings in this exploratory study, anxiety-a potentially modifiable factor-and age may be contributing factors for workforce unavailability in PD. However, prospective studies are warranted to confirm the findings and the causation of the association between anxiety and workforce unavailability needs to be clarified.
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4.
  • Wenning, Gregor K, et al. (författare)
  • Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease
  • 1997
  • Ingår i: Annals of Neurology. - : John Wiley and Sons. - 1531-8249 .- 0364-5134. ; 42:1, s. 95-107
  • Tidskriftsartikel (refereegranskat)abstract
    • Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.
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5.
  • Brundin, Patrik, et al. (författare)
  • Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
  • 2000
  • Ingår i: Brain. - : Oxford University Press. - 1460-2156 .- 0006-8950. ; 123, s. 1380-1390
  • Tidskriftsartikel (refereegranskat)abstract
    • Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
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6.
  • Martinez-Martin, Pablo, et al. (författare)
  • EuroInf: A Multicenter Comparative Observational Study of Apomorphine and Levodopa Infusion in Parkinson's Disease
  • 2015
  • Ingår i: Movement Disorders. - : John Wiley and Sons. - 0885-3185. ; 30:4, s. 510-516
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson's disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared 43 patients on Apo (48.8% males, age 62.3 +/- 10.6 years; disease duration: 14 +/- 4.4 years; median H & Y stage 3; interquartile range [IQR]: 3-4) and 44 on IJLI (56.8% males, age 62.7 +/- 9.1 years; disease duration: 16.1 +/- 6.7 years; median H & Y stage 4; IQR, 3-4). Cohen's effect sizes (0.8 considered as large) were large with both therapies with respect to total motor, nonmotor, and quality-of-life scores. The Non-Motor Symptoms Scale (NMSS) with Apo showed moderate improvement, whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the NMSS showed significantly higher improvement with IJLI. Seventy-five percent on IJLI improved in their quality-of-life and nonmotor symptoms (NMS), whereas in the Apo group, a similar proportion improved in quality of life, but 40% in NMS. Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on this open-label, nonrandomized, comparative study, we report that, in advanced Parkinson's patients, both IJLI and Apo infusion therapy appear to provide a robust improvement in motor symptoms, motor complications, quality-of-life, and some NMS. Controlled, randomized studies are required. (c) 2014 International Parkinson and Movement Disorder Society
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7.
  • Ji, Sun-Gou, et al. (författare)
  • Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
  • 2017
  • Ingår i: Nature genetics. - 1546-1718. ; 49
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10(-15)). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10(-15)). Our study represents a substantial advance in understanding of the genetics of PSC.
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8.
  • Bergquist, Filip, et al. (författare)
  • [Parkinson's disease - heterogeneous and complex in its clinical presentation].
  • 2020
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • Parkinson's 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 Parkinson's 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 Parkinson's disease.
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9.
  • Danenberg, P. V., et al. (författare)
  • Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action
  • 2016
  • Ingår i: Critical Reviews in Oncology Hematology. - 1040-8428. ; 106, s. 118-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Folates have been used with cytotoxic agents for decades and today they are used in hundreds of thousands of patients annually. Folate metabolism is complex. In the treatment of cancer with 5-fluorouracil, the administration of folates mechanistically leads to the formation of [6R]-5,10-methylene-tetrahydrofolate, and the increased concentration of this molecule leads to stabilization of the ternary complex comprising thymidylate synthase, 2'-deoxy-uridine-5'-monophosphate, and [6R]-5,10-methylene-tetrahydrofolate.The latter is the only natural folate that can bind directly in the ternary complex, with other folates requiring metabolic activation. Modulation of thymidylate synthase activity became central in the study of folate/cytotoxic combinations and, despite wide use, research into the folate component was neglected, leaving important questions unanswered. This article revisits the mechanisms of action of folates and evaluates commercially available folate derivatives in the light of current research. Better genomic insight and availability of new analytical techniques and stable folate compounds may open new avenues of research and therapy, ultimately bringing increased clinical benefit to patients. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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10.
  • Kader, M., et al. (författare)
  • Mobility device use in people with Parkinson's disease : A 3-year follow-up study
  • 2018
  • Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 138:1, s. 70-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: This study aimed to investigate how the use and perceived unmet need of mobility devices (MD) in people with Parkinson's disease (PD) evolve over a 3-year period. Methods: The study reports baseline assessments (n = 255) and comparisons for participants with complete data at baseline and the 3-year follow-up (n = 165). Structured questions addressed the use and perceived unmet need of various MDs indoor and outdoor (eg, canes, wheeled walkers, and manual and powered wheelchairs). McNemar tests were used to investigate differences over time. Results: In the total sample at baseline, 30% and 52% of the participants reported using MDs indoors and outdoors, respectively. Among those with complete data also at the 3-year follow-up, the proportion of participants using MDs increased significantly (P < .001) from 22% to 40% for indoors and from 48% to 66% for outdoors, with transition of MD toward more assistive potential (ie, wheeled walker and manual wheelchair). Wheeled walkers were the most commonly used MD indoors as well as outdoors on both occasions. Among the users of multiple MDs, the most common combination was cane and wheeled walker on both occasions. The proportion of participants who reported a perceived unmet need of MDs was 5% at baseline, whereas it was 21%, 3 years later. Conclusions: The use and perceived unmet need of MDs in people with PD increase over time. There is a need for addressing MDs at clinical follow-ups of people with PD, with continuous attention in primary health care and municipality contexts.
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  • Resultat 1-10 av 62
  • [1]234567Nästa

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