Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to evaluate the contribution of central dopaminergic mechanisms to the P300 event-related potential (P300) abnormality in Parkinson's disease. We measured the P300 in 37 non-demented patients with Parkinson's disease (19 de novo and 18 levodopa-treated) and 15 age-matched healthy volunteers. The P300 measurement was repeated in 14 de novo patients, after 6-12 months levodopa therapy. The severity of parkinsonian symptom was assessed using the UPDRS-motor scale. De novo patients showed prolonged P300 latency compared with levodopa-treated patients, as well as healthy volunteers. The levodopa therapy for 6-12 months significantly shortened the P300 latency and reduced the UPDRS-motor examination score in de novo patients. However, the percent changes in the P300 latency were not correlated with those in the UPDRS-motor examination score. These results indicate that the central dopaminergic mechanisms apart from those responsible for motor symptoms, may contribute to the P300 abnormality in Parkinson's disease.
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PMID:Dopaminergic influences on the P300 abnormality in Parkinson's disease. 966 83

Which drugs to use when initiating pharmacotherapy in early Parkinson's disease (PD) is a complex treatment decision that depends on factors such as disease severity, functional disability, and psychosocial handicap, as well as individual aspects of age, employment status, cognitive impairment, and co-morbidity. Without clear proof of a drug's capacity to markedly alter or even stop progression of the disease, there is no pharmacologic strategy that can be currently viewed as universal first-line treatment. Dopamine (DA) replacement strategies offer greatest symptomatic relief and are needed whenever there is significant functional disability. All currently available oral DA agonists have been shown to be less effective and less well tolerated than levodopa. This has also been shown in recent double-blind controlled studies for the novel agonists such as ropinirole or cabergoline, although they appear equally effective in mild disease for the first 6-12 months of therapy. Taking into account the significant difference in cost between levodopa and DA agonists, there is at present no reason to universally start DA replacement therapy with a DA agonist in most patients. Dopamine agonists remain first-line treatment only for those at particular risk for developing levodopa-induced dyskinesias, i.e., young-onset PD patients.
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PMID:Should treatment of Parkinson's disease be started with a dopamine agonist? 971 76

Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson's disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6-12 months after surgery. The mean voltage 1 week postoperatively was 1. 45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.
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PMID:Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. 1085 80

Ventrolateral (VL) thalamotomy produced a marked reduction of oscillations related to the supraspinal components of Parkinson's disease tremor (4-7 Hz) and physiological tremor (8-12 Hz). Finger tremor was examined in nine patients undergoing unilateral VL thalamotomy and in nine age-matched controls. In comparison to the preoperative state, the relative percentage of power within the 7.6-12.5 Hz band did not increase after the surgical procedure. Furthermore, the amount of absolute power within the 7.6-12.5 Hz band was much lower for post-surgical patients in comparison to matched controls when periods of tremor having equal amplitudes were compared. These results suggest that VL thalamotomy interrupts a common circuit involved in the supraspinal component of both physiological and pathological tremors. We provide evidence that the thalamus may be involved in circuits generating physiological tremor in humans.
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PMID:Evidence that ventrolateral thalamotomy may eliminate the supraspinal component of both pathological and physiological tremors. 1085 46

The aim of the study was to determine the prevalence of visual hallucinations among hospice inpatients, and the prevalence of a number of possible associated risk factors. One hundred consecutive admissions to St. John's Hospice in Wirral were screened for visual hallucinations in a semi-structured interview. The prevalence of opioid administration, other drugs known to cause hallucinations, brain tumours, liver metastases, bone metastases, lung metastases, known renal failure, eye disease, Alzheimer's disease, Parkinson's disease, other neurodegenerative disorder, psychiatric disorder and epilepsy were also recorded. Subjects were screened for cognitive function using the Folstein mini-mental state examination (MMSE). Survival times from assessment to death were calculated. The results were analysed using arithmetical means with 95% confidence intervals (CI) and odds ratios with 95% confidence intervals. Almost half (47%) the patients had experienced visual hallucinations within the previous month. Hypnagogic or hypnopompic hallucinations of a person standing by the bedside were the commonest type. Median survival time for hallucinators was 15 days (range 0-50 days) and for non-hallucinators was 11 days (range 0-89 days). There was no significant difference in cognitive scores between hallucinators and non-hallucinators. Hallucinations were associated with multiple possible risk factors in every case. Hallucinators were more likely to be taking opioids, although the association was not strong (odds ratio 4.48, 95% CI = 1.6-12.19), and were taking larger numbers of potentially hallucinogenic drugs. It is not clear why some patients on opioids hallucinate and others do not. Data on the prevalence of various possible risk factors yielded ample material for the planning of future studies.
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PMID:Visual hallucinations: a prevalence study among hospice inpatients. 1121 63

The study aimed to compare olfactory function in idiopathic Parkinson's disease (IPD) and nonidiopathic Parkinson's syndrome (PS). At their first visit 50 PS patients (age 38-80 years) received testing for odor threshold, olfactory discrimination and identification. All patients underwent extensive neurological diagnostics including PET scans. Patients were followed up for 6-12 months. Most of IPD patients were functionally anosmic (n=19), the remaining IPD patients had severe/moderate hyposmia (n=18). PS patients diagnosed with multiple system atrophy had less severe olfactory deficits (7 hyposmia, 1 normosmia). With the exception of 1 hyposmic patient, other PS patients had no olfactory deficits (progressive supranuclear palsy, corticobasal degeneration, psychogenic PS, essential tremor). This study added to previous findings: (1) there was no major difference betwesen olfactory function in IPD subtypes; (2) all olfactory tests differentiated IPD from nonIPD. These data suggest that olfactory probes improve the diagnostic armamentarium in IPD.
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PMID:Olfactory function in Parkinsonian syndromes. 1238 7

To estimate an accurate annual incidence of Parkinson disease in Wakayama, a mail survey was conducted in 1998. A questionnaire was delivered to each clinic where Parkinson disease would be potentially diagnosed. The survey was conducted in February 1998 by the Research Committee on Parkinson disease of Wakayama. A total of 792 clinics and 87 hospitals were listed as candidates. Physicians in these 879 medical facilities were asked and instructed to register all newly diagnosed patients with Parkinson disease in 1997 according to the diagnostic criteria proposed by the Japanese Research Committee on Neuro-degenerative Diseases. Of 879 facilities, 873 ones including 81 hospitals replied (response rate: 99%). A total of 229 patients were reported as newly diagnosed cases in 1997. Of these cases, 183 cases were classified as Yahr I to III. The annual incidence rate was 16.9 per 100,000 population (95% confidence interval: 14.5-19.3). Male-to-female ratio was 1:1.4 as a whole, and the dominant age stratum was 70 to 79 years old. When Parkinson disease incidence was observed from northern part of Wakayama to south by district, crude rates (95% CIs) were 15.9(12.9-18.9), 18.1(12.0-24.2), and 19.3(13.4-25.2). After age-adjustment using the Japanese Model Population in 1985, differences of Parkinson disease incidence became attenuated and adjusted rates (95% CIs) turned to 10.8(9.1-12.7), 10.4(8.6-12.2), and 9.9(6.9-12.9), respectively.
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PMID:Incidence of Parkinson disease in Wakayama, Japan. 1246 74

In 1995, it was suggested that immature stem cells (Berashis Cells) existing in human cord blood might have an ameliorating effect on such neurological diseases as Alzheimer's, amyotrophic lateral sclerosis and Parkinson's disease. Since these predictions, we have been able to successfully extend the length of life of mice with amyotrophic lateral sclerosis [B6SJL-TgN(SOD1-G93A)IGUR], Huntington's Disease (B6CBA-TgN(H.Dexon1)62Gpb and Alzheimer's mice [Tg(HuAPP695.SWE)2576]. Recently we expanded the studies to include mice with Parkinson's Disease. 32 mice, 6-12 weeks old B6CBACa-AW-J/A-Kcnj6<wv> were obtained from Jackson Laboratory, Bar Harbor, Maine. The mice were divided into 3 groups: (A) 10 untreated control mice, (B) 10 mice treated with 5.6 x 10(6) congenic bone marrow mononuclear cells and (C) 12 mice receiving 100-110 x 10(6) HUCB mononuclear cells intravenously. No immunosuppression was used. When 50% of the controls were dead only 1 of the 10 mice receiving congenic marrow and 2 out of 12 mice that received cord blood mononuclear cells were dead. This preliminary study was terminated when the animal's were 200 days old, at that time one out of 10 controls was alive. Out of 10 mice that received congenic bone marrow, 2 were alive. Out of 12 mice that received megadoses of cord blood mononuclear cells 4 were alive. Survival curve of mice that had congenic marrow had a p value of <.05; the survival curve of mice receiving cord blood mononuclear cells had a p value <.001 (Fig 1) compared to controls. Human umbilical cord blood mononuclear cells significantly delayed the onset of symptoms and death of Parkinson's disease mice. This effect was greater than that produced by congenic bone marrow cells.
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PMID:Parkinson's disease mice and human umbilical cord blood. 1293 16

Current medical and surgical therapies for Parkinson's disease provide symptomatic control of motor impairments rather than slowing or halting the progression of the disease. Previous clinical trials examining drugs such as dopamine agonists and selegiline for neuroprotective effects used "surrogate" outcomes, including clinical measures (rating scales, time to require levodopa), neuroimaging techniques (beta-CIT single photon emission computed tomography; fluorodopa positron emission tomography), and mortality tracking. These studies failed to provide conclusive results because of design faults such as failing to control for symptomatic effects, small sample size, and not accounting for the possible effects of drugs on radionuclide tracer handling. Lessons must be learned from these failed neuroprotection trials. This review summarises the problems with previous neuroprotection studies and makes recommendations for future trial design. It is concluded that the primary outcome of explanatory trials should continue to be clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS). It should be assumed that all agents have a symptomatic effect, which necessitates evaluation after a prolonged drug washout period. To achieve the evaluation after a prolonged drug washout period more effectively, trials must be performed in early disease and over a short period (6-12 months) so that symptomatic therapy is not required. To achieve adequate statistical power, these trials will need to include thousands of patients. Radionuclide imaging can only be used in such trials after considerable methodological work has been performed to establish its validity and reliability. To be affordable, such large explanatory trials need more streamlined designs with fewer hospital visits, fewer outcome measures, and rationalised safety monitoring. The clinical effectiveness of promising compounds from explanatory trials will need to be established in large long-term pragmatic trials using outcome measures such as quality of life, cost-effectiveness, and mortality. Such pragmatic trials could be continuations of the explanatory trials: after the primary outcome of the explanatory study (e.g., UPDRS) has been reported in an interim analysis, the trial could be continued for a further 5 to 10 years to report on quality of life and health economics outcomes.
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PMID:A "cure" for Parkinson's disease: can neuroprotection be proven with current trial designs? 1513 11

Ergot derivative dopamine agonists, e.g. pergolide, bromocriptine, dihydroergocriptine used in treatment of Parkinson's disease can cause pleural, pericardial, retroperitoneal and valvular fibrotic changes. Case No 1: A 56-year-old woman with PD was treated with pergolide 3mg/24h since July 2002. In June 2003, edema of lower extremities was first noticed and echocardiography found a minor mitral regurgitation without any morphological changes of the valve. In January 2004, left- sided cardiac failure rapidly developed and echocardiography revealed multivalvular insufficiency with predominating severe mitral regurgitation. Mitral valve replacement was performed and pergolide was changed to ropinirole. Until now, neither cardiac functions nor motor status are sufficiently compensated. Case No 2: A 66-year-old-man with PD since 1996 was treated with pergolide 3 mg/day since 1999. In the beginning of 2004, leg edema appeared. On examination, bilateral hydronephrosis with ureteric strictures and incipient renal insufficiency was found. Bilateral ureteroplasty was performed and the histology showed periureteric fibrosis. Treatment with steroids was initiated and pergolide was changed to pramipexole. Despite the treatment, the fibrosis progressed, requiring ureteral stenting. Based on the literature review and on our own experience, we propose following guidelines to minimize the risk of complications: A. Not to use EAD as the first-line dopamine agonists. B. Regularly follow all patients treated with EAD, especially monitor the majorsymptoms: dyspnea, cough, fatigue, leg edema (also asymmetric), symptoms of urinary outflow obstruction, cardiac insufficiency, chest pain, heart murmur. An elevated ESR, C-reactive protein or anemia support the diagnosis. C. All symptomatic patients should undergo workup for serosal fibrosis (according to type of complication): chest X-ray or CT scan, spirometry, renal functions, renal ultrasound, CT of retroperitoneum. D. Before the introduction of EAD therapy, examine the renal functions, perform chest X-ray and echocardiography. Screening echocardiography should be performed in 3-6 months and subsequently in every 6-12 months.
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PMID:[Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?]. 1580


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