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)

The clues vary, and many of the "typical" signs are misleading or even contradictory. One patient acts impetuously while another seems to have lost his spontaneity. Still another shows aggressive, animalistic behavior--or becomes apathetic, perhaps curling up in the fetal position or sucking, rooting, or grasping as an infant does. Some patients can memorize and recite a long list of numbers, remember events of the day before, and recall many of their childhood experiences--yet they "forget to remember" why they went to the store. When this happens, it's likely that the frontal lobe isn't performing its goal-orienting function as it should. If a patient takes small steps, has trouble initiating a step, or can't seem to find and keep his center of gravity--or if he involuntarily resists or aids an attempt to move his neck, arms, or legs--he doesn't necessarily have Parkinson's disease; he may have a frontal lobe lesion instead. Usually--but not always--the easiest way to find out is to check for a resting tremor.
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PMID:Exploring the enigmas of frontal lobe dysfunction. 82 57

To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for < or = 6 months was undertaken. Patients were randomized into two parallel groups (LD alone and LD plus Br). During the first placebo-controlled stage of the study lasting 8 months, association of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Br, there was a tendency toward smaller daily requirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of continuous treatment in the 40 patients still enrolled in the open-label stage. At that point in time, the mean dose of Br had been increased by 9.2 mg in the combined treatment group, and the mean dose of LD was 40.7% lower than in the group receiving LD alone. On subsequent evaluations, the number of patients with dyskinesias or describing wearing-off fluctuations severe enough to require changes in treatment was lower than in the group under combined therapy, the differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but no conclusions can be drawn as to whether this dopamine agonist exerts a preventive effect on the late side effects of LD or has another mechanism of action.
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PMID:Early combination of bromocriptine and levodopa in Parkinson's disease: a prospective randomized study of two parallel groups over a total follow-up period of 44 months including an initial 8-month double-blind stage. 903 75

We discuss two types of age-associated diseases; aging-dependent such as Alzheimer's disease and congestive heart failure which increase logarithmically with age, versus age-dependent such as multiple sclerosis and amyotrophic lateral sclerosis which occur at proscribed ages, and then occurrence of new cases ceases or diminishes with further aging. Prevention strategies with both types emphasize postponement or delay of onset. The non-fatal aging-dependent diseases and conditions are an accumulating burden as we age, and increase overall morbidity in late years. These include Alzheimer's disease and other dementias, Parkinson's disease, loss of vision and hearing, incontinence, osteoporosis and hip fracture, osteoarthritis and depression. With mortality postponed, we will be living for many years at old and vulnerable ages. Life's quality will be reasonable for most. Still, increasing the chance that all will experience this desirable outcome requires pursuing the means to delay the onset of the physical and social events which we categorize as the non-fatal aging-dependent diseases and conditions. We must recognize that each added year occurs at the tip of an exponential curve where risk is maximal.
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PMID:Age-associated diseases and conditions: implications for decreasing late life morbidity. 1140 87

Lower cancer risk in Parkinson's disease (PD) patients compared to the general population has been reported. However, most of the studies were based on death certificates. We designed a case-control study to estimate the association of tumor preceding PD onset and PD. PD patients were matched by age and gender to PD-free individuals, randomly selected from the municipalities of residence of cases. Occurrence of tumors preceding PD onset was assessed through a structured questionnaire. Neoplasms were categorized as benign, malignant, or of uncertain classification, and endocrine-related or not. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for tumor categories and risk factors. We included 222 PD patients. Frequency of cancer was 6.8% for cases, 12.6% for controls. PD patients had a decreased risk for neoplasms (adjusted OR, 0.4; 95% confidence interval [CI], 0.2-0.7). Risk was reduced only for women (adjusted OR, 0.3; 95% CI, 0.1-0.7). PD patients had a decreased risk both for malignant (adjusted OR, 0.6; 95% CI, 0.1-2.5) and nonmalignant neoplasms (adjusted OR, 0.3; 95% CI, 0.1-0.7). Still, risk was decreased for endocrine-related tumors (adjusted OR, 0.3; 95% CI, 0.1-0.9) and non-endocrine-related tumors (adjusted OR, 0.4; 95% CI, 0.1-0.9). Our study confirms the inverse association between PD and neoplasms reported in previous epidemiologic studies.
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PMID:Tumor diagnosis preceding Parkinson's disease: a case-control study. 1525 39

Current therapies for Parkinson's disease (PD) are limited in their ability to control PD symptomatology, are associated with motor and psychiatric side effects, and do not prevent disease progression. Considerable scientific and media interest has focused on the potential value of gene and stem cell therapies to overcome these problems and to enhance the quality of life for PD patients. Gene therapies utilize a viral vector to deliver a protein of interest to specific brain region. Clinical trials of gene therapy are currently underway using adeno-associated virus to deliver AADC to the striatum, the trophic factor nurturin to the striatum, and GAD to the STN. To date, no serious adverse effects have been noted, but only a small number of patients have been studied. Stem cells are pluripotential cells that offer the potential of generating unlimited numbers of optimized dopamine cells for transplantation. Stem cells can be grown and expanded in tissue culture and then induced to differentiate into dopamine neuronal phenotypes. Transplantation of these cells into the striatum is associated with behavioral improvement in 6-OHDA rodents and MPTP monkeys. Still, only small numbers of transplanted dopaminergic cells survive, and benefits are modest. Clinical trials in PD have not yet been performed. There is considerable enthusiasm for the potential of these procedures, but there remains much to learn in the laboratory and neither has been established to be effective as a treatment for PD. Long term safety and efficacy trials have not been performed in PD patients and the potential of unanticipated side effects must be addressed. Further, neither treatment is expected to improve the non-dopaminergic features of PD.
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PMID:Gene transfer of trophic factors and stem cell grafting as treatments for Parkinson's disease. 1671 56

Gene therapy for Parkinson's disease has become a clinical reality with three different approaches currently being tested in patients. All three trials employ an adeno-associated virus with a type two serotype (AAV2). To date, no serious adverse events related to the injections of therapeutic vectors have been reported in any patient. This safety profile was predicted based upon, in some cases, exhaustive preclinical testing in both rodent and primate species. Still some argue that regulatable promoters are required so that expression of the transgene can be halted should untoward side effects arise. We argue that given the current empirical data base of AAV2, the lack of regulatable promoters that have been proven to be safe and effective, and the pressing clinical needs of PD patients, the mandatory use of regulatable vectors is not only unnecessary but, in some instances, misguided and potentially dangerous. This commentary will outline the issues related to the use of regulatable promoters for gene therapy for PD and express our opinion as to why mandating the use of such promoters might result in outcomes that are unsafe, unproductive, and counter to the progress of scientifically sound, clinical research.
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PMID:Regulatable promoters and gene therapy for Parkinson's disease: is the only thing to fear, fear itself? 1788 24

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder and is characterized by a continuous and selective loss of dopaminergic neurons in the midbrain with a subsequent reduction of the neurotransmitter dopamine in the striatum. Strategies to overcome limitations of conventional symptomatic treatment have employed cell-based strategies including transplantation of developing neural tissue or neural stem cells (NSCs) into the degenerated host brain. Still there is a tug of war for determining the ideal cell source for transplantation strategies. ES cells have the widest and most blatant potential to become the winner because they promise to be made in high quantities and to hold large amounts of the desired cell type. Adult and fetal neural stem cells have the capacity to self-renew and they are able to differentiate into all major cell-types of the brain without bearing tumorigenic potential. They can be isolated and expanded in vitro for a long time retaining the potential to differentiate into important neural cell types including dopaminergic neurons. Another source for cell-replacement are bone marrow stromal cells (MSCs). These cells can be converted into a cell type with all major features of NSCs. Efforts are made to improve these cell sources for transplantation or finding new cell sources like induced pluripotent stem cells (iPS). However, novel grounds are broken: bridging transplantations might improve the clinical outcome by restoring the nigro-striatal pathway and recruitment of endogenous stem cells by pharmacological manipulations uses the inherent regenerative potential of the diseased brain. This review discusses recent data on stem cell technology with respect to cell replacement strategies in PD as well as endogenous dopaminergic regeneration.
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PMID:Restorative approaches in Parkinson's Disease: which cell type wins the race? 1973 67

The relationship between Restless Legs Syndrome (RLS) and Parkinson's disease (PD) is still controversial. Most genetic, pathological, and imaging data argue against a close association of these two disorders. Still, many studies reported an increased prevalence of RLS in PD patients. These studies are difficult to interpret because the current diagnostic criteria for RLS have not been validated in PD patients. Although many PD patients suffer from motor restlessness due to parkinsonism and may thus mimic RLS, the risk for (secondary) RLS in PD patients is probably slightly increased. This review provides an overview of the current pertinent literature and discusses the possible association between RLS and PD.
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PMID:Restless Legs Syndrome (RLS) and Parkinson's disease (PD)-related disorders or different entities? 1975

The question of early, even premotor, detection of Parkinson's disease (PD) has become a major issue because the effect of neuroprotective therapies depends on the time they are started. A number of clinical premotor markers which are helpful especially in the early diagnosis are being discussed; however, they are mostly unspecific and already signs of the progressing neurodegenerative process. An increasingly important risk marker for PD is genetic predisposition, as the number of known disease causing and modulating genes is increasing. Still, only the minority of PD cases can be attributed to monogenetic forms. Substantia nigra (SN) hyperechogenicity, assessed by transcranial sonography, has been shown to be a typical marker for PD. Because of its stability during the disease course, this echofeature is very helpful in early and differential diagnosis. Moreover, functional neuroimaging studies indicate a vulnerability of the nigrostriatal system of yet healthy subjects with SN hyperechogenicity. This vulnerability may become clinically relevant with age, under neuroleptic therapy, or under demanding motor tasks. The fact that still unaffected mutation carriers for monogenetic PD show this echofeature and that over the years some subjects with SN hyperechogenicity have already been observed to develop PD indicates that it may be regarded as a risk factor--a hypothesis which is currently being investigated in large prospective investigations.
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PMID:Transcranial ultrasound as a risk marker for Parkinson's disease. 1987 99

The molecular mechanisms underlying the pathogenesis of idiopathic Parkinson's disease (PD) have not been completely elucidated; however, some progress has been made in identifying factors that compromise survival of the dopaminergic neurons in the substantia nigra (SN) the death of which give rise to the motor symptoms that enable clinicians to diagnose the disease in its mid- to late stages. The prevailing theory regarding processes that are likely to account for degeneration of the nigrostriatal system centers around mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation. Of these, neuroinflammation is one candidate that appears to accumulate more support with each passing year. A number of researchers have attempted to manipulate inflammation in various animal PD models with varying levels of success. Still others have used inflammatory stimuli to elicit nigral cell death (NCD), a disturbing finding that has prompted much interest. In this chapter, we attempt to integrate what is known about the role of neuroinflammation in PD with the factors we feel are critical for understanding how inflammation modulates disease progression.
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PMID:Modeling neuroinflammatory pathogenesis of Parkinson's disease. 2088 72


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