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Biomedical subjects

P Odin

Publications and source records attributed to P Odin.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of high-dose cabergoline in Parkinson's disease.

OBJECTIVES: To assess the efficacy and safety of high-dose (up to 20 mg/day) cabergoline in Parkinson's disease (PD) patients with motor fluctuations and/or dyskinesias. MATERIALS AND METHODS: Thirty-four PD patients had cabergoline up-titrated and their levodopa (L-dopa) reduced over a maximum of 20 weeks, followed by at least 6 weeks steady cabergoline dosing. Primary endpoint was change in mean hyperkinesia intensity at the final visit (week 26). RESULTS: Mean (+/- SD) cabergoline was increased from 6.43 +/- 2.66 to 12.78 +/- 5.67 mg/day and mean L-dopa reduced from 606.6 +/- 263.9 to 370.6 +/- 192.5 mg/day. A significant reduction (P < 0.001) in mean hyperkinesia intensity occurred from baseline (day 0) to week 26. Improvements in 'on with dyskinesias', mean dystonia intensity (P < 0.05), time spent in 'severe off' condition, severity of 'off' periods as well as clinical/patient global impression, and health-related quality of life were observed. Twenty-four drug-related adverse events were recorded of which four were regarded as serious. CONCLUSION: High-dose cabergoline was well tolerated and provided significant improvements in the Parkinson symptomatology and a reduced requirement for L-dopa.

Adolescent↗
PubMed2005

Distributed neural actions of anti-parkinsonian therapies as revealed by PET.

There is a limited understanding of how different anti-parkinsonian treatments act at the neuronal systems level. Using positron emission tomography we examined the effects of levodopa and deep brain stimulation of the subthalamic nucleus on patterns of regional cerebral blood flow in patients with Parkinson's disease during a homogenous cognitive-behavioural state rather than during an unspecified resting state. We found that when medicated precuneus, frontal, parietal, cerebellar and midbrain areas were relatively more activated than when stimulated, whereas when stimulated the precentral gyrus, caudate and thalamus were relatively more activated than when medicated. Areas that were activated by both treatments included the temporal gyri, anterior thalamus, and midbrain. Regions of prefrontal cortex showed relatively greater activation in the "off treatment" conditions of both the medicated and stimulated groups. Our findings suggest that the two treatment methods may lead to symptomatic relief via both common and different sites of action.

Aged↗
PubMed2005

Retrospective evaluation of cardio-pulmonary fibrotic side effects in symptomatic patients from a group of 234 Parkinson's disease patients treated with cabergoline.

BACKGROUND: Cardiac valvulopathy has been recently associated with the use of the ergot dopamine agonist (EDA) pergolide in Parkinson's disease (PD). Cabergoline a widely used, well-tolerated EDA which has also been recently implicated in relation to fibrotic side effects although the evidence base for this is not sound. AIMS: In PD patients on chronic cabergoline therapy, do symptoms suggestive of serosal/cardiac fibrosis imply underlying fibrotic lesions? METHODS: A retrospective data review of 234 PD cases from three UK centres, on chronic cabergoline monotherapy or adjunctive treatment to identify symptoms suggestive of pleuro-pulmonary, cardiac or retroperitoneal fibrosis. These causes were thereafter selectively examined by appropriate specialists with relevant investigations. CONCLUSIONS: Out of 234 cases, 15 were identified with symptoms suggestive of respiratory, cardiac or abdominal systems involvement although subsequent investigations failed to reveal definite association with cabergoline except two cases with probable alveolitis and a possible association with cardiac murmur in one case. In spite of the deficiencies of a retrospective study, the results suggest a low risk of fibrotic side effects with cabergoline, particularly cardiac valvulopathy.

Adult↗
PubMed2004

Computerized movement analysis and beta-CIT-SPECT in patients with restless legs syndrome.

Considering the positive effect of dopaminergic treatment on Restless Legs Syndrome (RLS), it has been suggested that the cause of RLS may be linked to central dopaminergic dysfunction. As problems of alternating movements can result from a failure in the dopaminergic system, we used a movement analysis system to analyse this and in-parallel, performed [123I]beta-CIT-SPECT to investigate signs of dopaminergic dysfunction in patients with RLS. In 10 patients with idiopathic RLS, we conducted a three-dimensional computerized ultrasound-based movement analysis before a single dose of levodopa (L-dopa) was given and 90 minutes after the L-dopa challenge. In 6 of the 10 RLS patients, the striatal dopamine transporter system was studied with [123I]beta-CIT-SPECT. We did not observe any significant change in the movement pattern with the computerized movement analysis and no significant effect of L-dopa on the movement. We did not detect any significant differences between patients and normal controls regarding beta-CIT-signals in putamen or caudate nucleus, respectively. There was, however, a slight but significant change regarding the relative [123I]beta-CIT-SPECT binding in the putamen vs. the caudate nucleus. We conclude that the methods used could not detect any definite signs of changed central dopaminergic function in patients with RLS.

Aged↗
PubMed2004

Restless legs syndrome: an overview of the current understanding and management.

Over the last few years, major progress in research has improved our understanding of the restless legs syndrome (RLS). Although frequently under-diagnosed, several epidemiological studies have estimated its prevalence in western countries at 4-10% of the general population. Its diagnosis is usually made on a clinical basis, according to the criteria established by the International RLS Study Group (Mov Disord 1995; 10:634). Furthermore, major advances have also been achieved regarding our understanding of the pathophysiology of the disorder. Thus, several brain imaging studies, as well as pharmacological challenges, suggest the presence of a dopaminergic dysfunction playing a major role in its causation. In addition, a strong association has been discovered between brain iron deficiency and RLS. Eventually, dopaminergic drugs have shown therapeutic efficacy in various large-scale therapeutic trials, and, today, dopaminergic agonists represent the first line of treatment. In conclusion, these and other recent findings shed light on our understanding and management of one of the most common movement disorders.

Anemia, Iron-Deficiency↗
PubMed2003

Three-dimensional computerized analysis of diadochokinetic movements of Parkinsonian patients.

OBJECTIVES: Considering the rapid appearance of new pharmaceutical and surgical treatments for Parkinson's disease, a development of quantitative and objective methods for measuring treatment effects is highly warranted. The purpose of this study was to investigate the usability of a computerized movement analysis system in Parkinson's disease patients. MATERIAL AND METHODS: We analysed the effect of L-dopa in a group of 14 patients with idiopathic Parkinson's disease and compared the results to those of 14 control persons. The results were compared to those achieved with the UPDRS, Hoehn & Yahr and Schwab & England Scales, as well as, to time-measured manual testing according to the CAPIT and CAPSIT-PD protocols. RESULTS: We found that the computerized analysis results correlated well with the findings obtained with traditional scales and manual techniques, and that the computer-analysis had the advantage of delivering more exact and quantitative information not only concerning movement speed but also aspects of movement quality. CONCLUSION: We conclude that this form of computerized movement analysis can have an important role in evaluating the effect of treatments, individualizing the therapy, as well as, for diagnostic procedures in patients with Parkinson symptomatology.

Adult↗
PubMed2003

[[123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson's disease and multiple system atrophy.

AIMS: Definition of the regional pattern of dopamine transporter (DAT) dysfunction in advanced Parkinson's disease (PD) and evaluation of a potential correlation between DAT binding and symptoms; elucidation of the role of DAT imaging in the differential diagnosis of PD and multiple system atrophy (MSA); assessment and comparison of serotonin transporter (SERT) binding in PD and MSA. METHODS: [(123)I]beta-CIT SPECT was performed in 14 patients with advanced PD, 10 with moderate MSA and 20 healthy persons. Specific to nonspecific tracer binding ratios (V(3)") were calculated via ROI analysis of uptake images at 4 h (SERT binding) and 24 h (DAT binding) p. i. RESULTS: In PD bilateral reduction of striatal DAT binding (63-70%) was seen. The caudate ipsilateral to the clinically predominantly affected side showed relatively the least impairment. Significant correlations (r = -0.54 to -0.64) between DAT binding and Hoehn and Yahr stage, UPDRS-scores and duration of disease were found. In MSA DAT binding was less reduced (40-48%) targeting the putamen contralateral to the side of clinical predominance. Significantly lower SERT binding was observed in PD midbrain and MSA hypothalamus compared to controls -- and in MSA relative to PD mesial frontal cortex. CONCLUSIONS: In advanced PD striatal DAT binding is markedly reduced with the least reduction in caudate ipsilateral to the clinically predominantly affected side. In moderate MSA with asymmetrical symptoms DAT dysfunction is predominant in the contralateral putamen, a pattern seen in early PD. The reduction of SERT in the midbrain area of PD patients suggests additional tegmental degeneration while in MSA the serotonergic system seems to be more generally affected.

Brain↗
PubMed2002

Bone morphogenetic proteins but not growth differentiation factors induce dopaminergic differentiation in mesencephalic precursors.

Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) are potential therapeutic molecules for the treatment of Parkinson's disease (PO). Here we compare the effects of BMP3, 5, 6, and 7 and GDF5 and 6 in a rat mesencephalic cell culture system that reflects the developmental stage of neurons around birth. High concentrations of BMP5, 6, and 7 and GDF5 and 6 induced astroglial cell fate and a depletion of oligodendrocytes. Only BMP5, 6, and 7, however, significantly increased the number of tyrosine hydroxylase (TH)-positive neurons and induced nuclear translocation of the phosphorylated BMP-restricted Smad in a substantial number of TH- and microtubule-associated protein 2(MAP2ab)-positive cells. None of the proteins protected TH-positive cells against 6-hydroxydopamine-induced oxidative stress. BMP3 was without any effect throughout the studies. We conclude that BMP5, 6, and 7 act directly and independently on precursors of the dopaminergic and astroglial lineage and induce their differentiation. In contrast, GDF5 and 6 primarily affect nonneuronal cells in mesencephalic cultures of this stage.

Animals↗
PubMed2002

Current state of stem cell research for the treatment of Parkinson's disease.

Current findings suggest that multipotent stem cells may be suitable for cell replacement therapies in the treatment of neurodegenerative disorders. Embryonic stem (ES) cells are pluripotent cells isolated from the inner cell mass of the preimplantation blastocyst, which give rise to all cells in the organism. Similarly, multipotent stem cells are also able to regenerate, but are believed to have a more restricted potential than ES cells, and are often defined by the organ from which they are derived. Neural stem cells have been categorized as multipotent stem cells derived from the nervous system with the capacity to regenerate and to give rise to cells belonging to all three cell lineages in the nervous system: neurons, oligodendrocytes, and astrocytes. It is hoped that research on stem cells may reveal methods for producing an infinite supply of dopamine neurons for transplant into Parkinson's disease (PD) patients. The problem is controlling cell growth and differentiation. We will briefly review the current state of stem cell research and will critically discuss the potential of stem cells for the treatment of PD.

Brain Tissue Transplantation↗
PubMed2002

Restless legs syndrome.

Restless legs syndrome (RLS), first described in 1672 and given its name in 1945, is one of the most common sleep and movement disorders. Modern population-based studies demonstrate a prevalence between 5% and 15% in adult white populations. According to the diagnostic criteria, RLS is defined as an irresistable desire to move limbs, usually associated with paresthesias/dysesthesias and motor restlessness. The symptoms start or worsen at rest and improve with activity. Additionally, the symptoms worsen in the evenings and/or nights, which often results in disturbance of sleep with daytime tiredness. There is often a family history of RLS. Initially, the disease course is usually fluctuating and later may become continuous or chronic-progressive. The diagnosis is based on the patient history and is supported by a normal neurological examination. RLS is confirmed by the finding of periodic limb movements (PLM) in polysomnographic investigations and by a response to dopaminergic medication. A large number of studies have confirmed the effect of levodopa (L-dopa) in the treatment of RLS. A majority of the patients treated over a longer period of time with L-dopa, however, develop problems with an effect called augmentation, where the RLS symptoms begin appearing earlier during the day and involve new parts of the body with increasing severity. A large number of studies have now confirmed that dopamine agonists can also be effective in RLS therapy, and that this treatment seems to involve less risk for augmentation. This paper provides a general review of RLS with a focus on current treatment options.

Adult↗
PubMed2001

Intermuscular coherence in Parkinson's disease: relationship to bradykinesia.

We hypothesised that bradykinesia may be partly due to the failure of the corticomuscular system to engage in high frequency oscillatory activity in Parkinson's disease (PD). In healthy subjects such oscillations are evident in coherence between active muscles at 15--30 Hz. We therefore investigated the effects of therapeutic stimulation of the basal ganglia on this coherence and related it to changes in bradykinesia in the contralateral arm. Increases in coherence at 15--30 Hz and improvements in bradykinesia upon stimulation were correlated (r = 0.564, p < 0.001). This suggests that the basal ganglia modulate oscillatory activity in the corticomuscular system and that impairment of the motor system's ability to engage in synchronised oscillations at high frequency may contribute to bradykinesia in PD.

Electric Stimulation Therapy↗
PubMed2001

Intermuscular coherence in Parkinson's disease: effects of subthalamic nucleus stimulation.

It remains unclear how high frequency stimulation of the subthalamic nucleus (STN) improves parkinsonism. We hypothesized that stimulation may affect the organization of the cortical drive to voluntarily activated muscle. Normally this is characterized by oscillations at 15-30 Hz, manifest in coherence between muscles in the same frequency band. We therefore investigated the effects of STN stimulation on electromyographic (EMG) activity in co-contracting distal arm muscles in nine subjects with Parkinson's disease off drugs. Without stimulation, coherence between EMG signals was diminished at 15-30 Hz compared with nine controls. STN stimulation increased coherence in the 15-30 Hz band, so that it approached that in healthy subjects. The results suggest that STN stimulation facilitates the normal cortical drive to muscles.

Analysis of Variance↗
PubMed2001

Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [(18)F]FDG-PET.

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Adult↗
PubMed2001

Cardiovascular effects of domperidone in patients with Parkinson's disease treated with apomorphine.

OBJECTIVES: The cardiovascular effects of the peripheral dopamine D2-receptor antagonist domperidone were studied in patients with idiopathic Parkinson's disease treated with continuous subcutaneous infusion of apomorphine. MATERIAL AND METHODS: Blood pressure and heart rate of 10 patients were monitored for 24 h before and after treatment with domperidone using an automatic device for blood pressure recording. RESULTS: Blood pressure and heart rate increased significantly during 24 h of domperidone treatment. When day and night values were analysed separately, a significant difference of blood pressure between the groups was found only during the day whereas heart rate was significantly increased during both day and night. Domperidone shifted blood pressure and heart rate upwards without affecting the drop of blood pressure in the erect position. CONCLUSION: Domperidone increases blood pressure and heart rate without inducing nocturnal hypertension in apomorphine treated patients with idiopathic Parkinson's disease. Increased heart rate by domperidone is a new finding but the clinical significance is unclear and requires further investigation.

Aged↗
PubMed2001

Apomorphine in the treatment of Parkinson's disease.

Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist. Given subcutaneously, it has a rapid onset of antiparkinsonian action qualitatively comparable to that of levodopa. Despite its long history, it was not until peripheral dopaminergic side effects could be controlled by oral domperidone that the clinical usefulness of apomorphine in Parkinson's disease began to be investigated thoroughly in the mid-1980s. Although several routes have been tried, subcutaneous administration, either as intermittent injections or continuous infusion, is so far the best and most applied in the treatment of advanced, fluctuating Parkinson's disease. Clinical trials have shown stable efficacy with markedly reduced time spent in "off" phases as well as, for infusion therapy, reduced levodopa requirements. In the most successful cases, motor fluctuations disappear and the need for oral medication is eliminated. Adverse events are usually mild and dominated by cutaneous reactions. Neuropsychiatric side effects occur, but the influence of apomorphine on these remains controversial. Controlled long-term clinical trials are highly warranted to reveal the full potentials of this treatment. Careful patient selection and follow-up, where the specialized movement disorder nurse has a crucial role, are paramount for a successful long-term outcome. Apomorphine warrants a wider application in the treatment of advanced Parkinson's disease and should be tried before more invasive interventions are considered.

Antiparkinson Agents↗
PubMed2000

Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease.

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.

Adult↗
PubMed1999

Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

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.

Adult↗