Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources

Effect of Pd on the clinical performance of amalgam.

The purpose of this study was to determine the effect of a small amount of Pd on the clinical performance of a high-copper spherical-particle dental amalgam. Two identical alloys, with and without 0.5% Pd, were investigated. The marginal fracture, surface texture, and surface luster of 193 clinical restorations were evaluated at one year, those of 182 at two years, and those of 144 at three years of service. In vitro corrosion tests of anodic polarization and constant potential coulometry were also conducted. Over the three-year period, the results showed no differences in marginal fracture or surface texture between the two alloys. However, the alloy with Pd showed a significant superiority in surface luster over this time period. Both corrosion tests showed less electrochemical activity on the part of the alloy containing Pd.

Adolescent↗

Influence of dehydroepiandrosterone on G-6-PD activity and 3H-thymidine uptake of human lymphocytes in vitro.

Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring 3H-thymidine uptake. DHEA inhibited 3H-thymidine uptake of mitogen-stimulated cells from both G-6-PD+ and G-6-PD- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of 3H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

Cells, Cultured↗

Effect of L-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status.

BACKGROUND: The antiparkinsonian drug L-dopa causes increased cellular synthesis of homocysteine and consequent hyperhomocysteinemia in rats. This effect of L-dopa on plasma homocysteine is accentuated under conditions of impaired homocysteine metabolism such as folate deficiency. OBJECTIVE: To investigate the effect of L-dopa administration and B-vitamin status on plasma homocysteine concentrations in humans with PD. METHODS: Plasma homocysteine, folate, vitamin B(12), and pyridoxal-5'-phosphate (PLP) concentrations were determined in 40 individuals diagnosed with idiopathic PD who were being treated as outpatients at the Boston University Medical Center Neurology Clinic. Twenty of the patients were on L-dopa therapy (treatment group) and 20 were L-dopa-naive (control group). RESULTS: The mean plasma homocysteine concentration was higher in the treatment group than in the controls (p = 0.018). Plasma homocysteine was correlated with plasma folate, vitamin B(12), and PLP concentrations in the treatment group (p <or= 0.007) but not in the controls. CONCLUSION: L-Dopa can cause hyperhomocysteinemia in PD patients, the extent of which is influenced by B-vitamin status. The B-vitamin requirements necessary to maintain normal plasma homocysteine concentrations are higher in L-dopa-treated patients than in those not on L-dopa therapy. B-Vitamin supplements may be warranted for PD patients on L-dopa therapy.

Antiparkinson Agents↗

The differential effect of PD and normal aging on early explicit sequence learning.

BACKGROUND: Motor sequence learning is abnormal in PD. However, it is not known whether this defect is present during the earliest stages of the illness or whether it reflects specific limitations in dividing attention between cognitive and motor requirements. METHODS: Fifteen patients with early stage PD and 10 age-matched and 9 younger normal controls moved the right dominant hand on a digitizing tablet to eight targets presented on a screen in synchrony with a tone at 1-second intervals. The tasks were as follows: 1) CCW--a timed-response task where targets appeared in a predictable counterclockwise order; 2) RAN--a reaction time task where targets were random and unpredictable; 3) SEQ--a task with multiple demands emphasizing explicit learning and target anticipation in which subjects learned a sequence while reaching for targets; and 4) VSEQ--subjects learned a visual sequence without moving. RESULTS: CCW and RAN yielded similar results in all groups. In patients with PD, sequence learning was the same in SEQ and VSEQ and was slower compared to both control groups. In older controls, learning was faster in VSEQ than in SEQ, whereas younger controls learned equally fast in both tasks. CONCLUSIONS: Despite normal motor execution, the initial phases of sequence learning are impaired in early PD independent of task requirements, possibly reflecting reduced working memory. Learning was slower in older than younger controls only in tasks with multiple demands, presumably due to reduced attentional resources.

Adult↗

Head trauma preceding PD: a case-control study.

OBJECTIVE: To investigate the association of PD with preceding head trauma using a case-control study design. METHODS: The medical records-linkage system of the Rochester Epidemiology Project was used to identify 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. The complete medical records of cases and controls in the system were reviewed to detect preceding episodes of head trauma. RESULTS: The frequency of head trauma overall was significantly higher in cases than in controls (odds ratio [OR] = 4.3; 95% CI = 1.2 to 15.2). Compared with subjects who never experienced a trauma, subjects who experienced a mild head trauma with only amnesia had no increased risk; however, subjects who experienced a mild head trauma with loss of consciousness or a more severe trauma had an OR of 11.0 (95% CI = 1.4 to 85.2). Although not significant, head trauma resulting in hospitalization was more frequent in cases than in control subjects (OR = 8.0; 95% CI = 1.0 to 64.0). Whereas the OR was higher for men than women and for patients with later onset of PD than for patients with earlier onset, these differences were not significant. CONCLUSIONS: These results suggest an association between head trauma and the later development of PD that varies with severity. Although the OR is high (4.3), the population attributable risk is only 5% because head trauma is a relatively rare event.

Adult↗

A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD.

The future management of Parkinson's disease (PD) requires pharmacologic agents that do not lose efficacy with disease progression or induce dyskinesia and that are free of other dopaminergic side effects. A2A receptor antagonists may provide an opportunity to introduce nondopaminergic management of PD. A2A receptors are selectively localized in basal ganglia and to the indirect output pathway where they control GABA and acetylcholine release. The A2A antagonists are effective in rodent models of PD, reversing motor deficits in haloperidol-treated, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated, or reserpinized mice, and potentiating L-dopa-induced rotation in 6-hydroxydopamine-lesioned rats without inducing dyskinesia. Importantly, the selective A2A antagonist KW6002 reverses motor disability and increases locomotor activity in MPTP-treated primates without provoking dyskinesia established by previous exposure to L-dopa. In addition, KW6002 shows additive antiparkinsonian activity with L-dopa and the D2 agonist quinpirole in MPTP-treated primates without enhancing the intensity of dyskinesia. The data available suggest that A2A antagonists, such as KW6002, may be effective as monotherapy for the management of PD and that they will also produce additional benefit when administered in combination with L-dopa or dopamine agonist therapy.

Adenosine A2 Receptor Antagonists↗

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

BACKGROUND: Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. OBJECTIVE: To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. METHODS: Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. RESULTS: At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. CONCLUSION: Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

Aged↗

Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD.

OBJECTIVE: To reevaluate the effect of subthreshold repetitive transcranial magnetic stimulation (rTMS) on concurrent fine movement in PD. BACKGROUND: A previous study showed a beneficial effect of rTMS on the performance of six patients with PD on the Grooved Pegboard test. METHODS: The authors repeated this experiment in 11 patients with idiopathic PD who performed the test while the stimulating coil discharged continuously at 5 Hz, either over the contralateral motor cortex at just below the threshold for movement, or in the air near the head as a control. Patients were tested twice under both conditions. RESULTS: Although some patients performed faster with rTMS, others showed the opposite effect. There was no significant effect of rTMS in the group, nor did baseline performance or the order of conditions interact with the effect of rTMS. CONCLUSIONS: Based on this larger and more comprehensive study, simultaneous, 5-Hz subthreshold rTMS over the motor cortex does not have consistent or potentially therapeutic effects on movement in PD.

Aged↗

Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.

OBJECTIVE: To determine whether pergolide monotherapy provides symptomatic relief in early PD. BACKGROUND: Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as "add on" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available. METHODS: The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52). RESULTS: Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects. CONCLUSION: This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.

Aged↗

Time course of frontal somatosensory evoked potentials. Relation to L-dopa plasma levels and motor performance in PD.

OBJECTIVE: To verify whether the change in L-dopa plasma levels after a single dose of carbidopa/L-dopa 50/200 (controlled-release) transiently modifies frontal components of somatosensory evoked potentials (SEPs) in patients with PD in parallel with improvement of motor performance. BACKGROUND: Apomorphine, a potent dopamine-agonist drug, transiently increases frontal SEP components, which may be depressed in PD; however, relationships between clinical status, frontal SEPs, and therapy are still unclear. METHODS: Nineteen PD patients (mean age 65.9 years, range 52 to 77, responders to L-dopa therapy, were studied in the same day at times T0 (baseline predose level), T1 (presumed L-dopa peak time), and T2 (end of dose-induced motor response). The following were monitored: L-dopa plasma concentration, tapping test, reaction times, peak latency (with central conduction times), and amplitude of cervical, subcortical, as well as cortical parietal and frontal SEP components elicited by median nerve stimulation of the more clinically affected arm. RESULTS: The average amplitude of frontal components of PD patients was significantly reduced at T0 with respect to control subjects. A significant and transient amplitude increase of frontal SEPs was found at T1, in parallel with the L-dopa peak concentration and improvement in motor performance (tapping and reaction times), without significant changes in amplitude of parietal SEP waves. No latency shifts were observed in brain and spinal waves. CONCLUSIONS: L-Dopa may influence the responsiveness of the parkinsonian brain as assessed by frontal somatosensory evoked potentials. The time course of these modifications coincides with that of the clinical response in the motor performance.

Aged↗

Transplantation of embryonic porcine mesencephalic tissue in patients with PD.

OBJECTIVE: To assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (VM) tissue in advanced PD. METHODS: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and 18F-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method on peripheral blood mononuclear cells. RESULTS: Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson's Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. 18F-levodopa PET failed to show changes on the transplanted side. CONCLUSIONS: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.

Aged↗

A multicenter randomized controlled trial of remacemide hydrochloride as monotherapy for PD. Parkinson Study Group.

BACKGROUND: Preclinical evidence suggests that manipulation of the glutamatergic system may provide an alternative strategy for therapeutic intervention in PD. Remacemide hydrochloride is a low affinity NMDA channel blocker that might improve parkinsonian symptoms by modulating glutamatergic overactivity in the basal ganglia or slow worsening by decreasing excitotoxicity. METHODS: The authors performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of remacemide in patients with early PD who were not yet receiving levodopa or dopamine agonists. The primary objective was to assess the short-term tolerability and safety of three dosage levels of remacemide. Two hundred patients were randomized to receive either remacemide 150 mg, 300 mg, or 600 mg, or matching placebo daily for 5 weeks. RESULTS: Significantly fewer patients receiving remacemide 600 mg daily were able to tolerate 5 weeks of their assigned treatment on a BID schedule compared with patients receiving placebo (64% versus 94%, p = 0.0002). Most patients who experienced intolerable side effects on the BID schedule, however, could tolerate the same daily dosage on a QID schedule. The most common adverse events were dizziness and nausea. There were no serious adverse events or clinically significant treatment-related changes in vital signs, laboratory values, or electrocardiograms. There was no evidence of improvement in PD signs or symptoms associated with remacemide monotherapy. CONCLUSION: Remacemide was generally well tolerated and safe in this 5-week trial. There was no evidence for a symptomatic effect of remacemide monotherapy in patients with early PD. Based on its favorable safety profile and several animal studies, further studies of remacemide are warranted as symptomatic therapy in levodopa-treated patients and as a neuroprotective agent.

Acetamides↗

Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD.

Plasma homocysteine and cysteine levels were measured in 90 patients with PD with the MTHFR C677T (T/T) genotype. The authors found that the levels of homocysteine-a possible risk factor for vascular disease-were elevated by 60% in levodopa-treated patients with PD, with the most marked elevation occurring in patients with the T/T genotype. Cysteine levels in subjects with PD did not differ from levels in control subjects. In the T/T genotype patients, homocysteine and folate levels were inversely correlated. Increased homocysteine might be related to levodopa, MTHFR genotype, and folate in PD.

Aged↗

[18 F]-dopa PET study in patients with juvenile-onset PD and parkin gene mutations.

+Parkin gene mutations cause a form of early-onset autosomal recessive PD with neuronal loss in the substantia nigra and no Lewy bodies. The authors present a PET [18F]-dopa study of one familial and two sporadic cases with juvenile-onset PD resulting from parkin gene mutations. They found a profound decrease of [18F]-dopa uptake, representing 28% of putamen and 44% of caudate nucleus control subject values. PD caused by parkin gene mutations is distinct from idiopathic PD on molecular grounds but has similar clinical and PET findings.

Adult↗

Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial.

BACKGROUND: The long-term effectiveness of three different initial drug regimes in patients with early, mild PD was evaluated by the PD Research Group of the United Kingdom (PDRGUK). In 1995, the selegiline arm of the trial was terminated following an interim analysis. METHOD: This was an open, randomized trial. Between 1985 and 1990, 782 patients with de-novo PD were recruited and randomized to one of three treatment arms: levodopa plus dopa decarboxylase inhibitor; levodopa plus decarboxylase inhibitor and selegiline; or bromocriptine. The main endpoints were mortality, disability, and adverse events. Intention-to-treat analysis was used. RESULTS: There was no significant difference in mortality between the bromocriptine and the levodopa arms (hazard ratio 1.15 [95% CI 0.90, 1.47]). Patients initially randomized to bromocriptine had slightly worse disability scores throughout follow-up. This difference was significant during the first years. Patients in the bromocriptine arm returned to pretreatment disability levels one year earlier than those in the levodopa arm. Patients randomized to bromocriptine had a significantly lower incidence of dyskinesias than those randomized to levodopa (rate ratio 0.73 [95% CI 0.57, 0.93]). However, this difference was not significant when only moderate to severe dyskinesias were considered. Patients in the bromocriptine arm had slightly lower rates of dystonias and on-off fluctuations, but moderate and severe forms were equally frequent in both arms. CONCLUSION: Starting treatment with the dopamine agonist bromocriptine does not reduce mortality in PD. A slightly lower incidence of motor complications is achieved at the expense of significantly worse disability scores throughout the first years of therapy.

Antiparkinson Agents↗

Novel three-stage ascertainment method: prevalence of PD and parkinsonism in South Tyrol, Italy.

BACKGROUND: A number of community-based studies on the prevalence of PD have been conducted worldwide, but they are often extremely costly and time consuming. OBJECTIVE: To assess the prevalence of PD and parkinsonism for the population aged between 60 and 85 years in South Tyrol, Northern Italy, using a novel population-based three-stage ascertainment method. METHODS: Seven hundred fifty persons aged 60 to 85 years from South Tyrol received a validated screening mail questionnaire for parkinsonism. In the second stage of the ascertainment method, trained primary care physicians (PCP) identified all persons with possible parkinsonism among those screened positive. In the third stage, movement disorders specialists excluded or confirmed the diagnosis in all identified people. RESULTS: The response rate was 87.6%. The prevalence rate per 100 population over 65 years of age was 1.5 (95% CI 0.6 to 2.3) for PD and 2.2 (95% CI 1.2 to 3.3) for parkinsonism after having been adjusted to the 1991 European standard population. Overall, 78% (95% CI 59 to 96%) of patients with parkinsonism were newly detected through the survey. CONCLUSIONS: The prevalence of PD and parkinsonism in people aged over 65 in South Tyrol was similar to that observed in door-to-door surveys in other European countries. The novel three-stage case ascertainment method employed proved a useful tool to substitute for expensive door-to-door surveys for prevalence studies of parkinsonism, detecting a high number of undiagnosed cases, particularly in geographically remote areas.

Aged↗

Parkinson's disease and sleepiness: an integral part of PD.

OBJECTIVE: To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents. METHODS: The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists. RESULTS: Sleep latency was 6.3 +/- 0.6 minutes (normal >8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal <10). A narcolepsy-like phenotype (> or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index >15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices. CONCLUSIONS: In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.

Aged↗

Restless legs syndrome and PD: a review of the evidence for a possible association.

Restless legs syndrome (RLS) is a common neurologic disorder whose prevalence has been estimated at 4 to 10% of the general population. Although its pathophysiology remains unknown, dopaminergic mechanisms are believed to play a central role. Furthermore, dopaminergic drugs have shown therapeutic efficacy in various large-scale therapeutic trials, and dopamine agonists now represent the first line of treatment. Several studies performed over the past years have suggested an association between RLS and Parkinson's disease (PD). However, the evidence is still limited and large controlled studies are needed to show the prevalence rates of PD in RLS patients versus controls. Furthermore, in contrast to PD, some brain imaging studies have revealed a mild striatal dysfunction in RLS. Preliminary neuropathologic evidence also suggests that the dopaminergic dysfunction does not involve neuronal degeneration at that level. Therefore, neuronal degeneration in other dopaminergic pathways than the nigrostriatal might be relevant in the pathogenesis of RLS in PD.

Brain↗