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)

Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.
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PMID:Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. 193 36

The most frequent psychic disturbances in Parkinson patients are reversible toxic psychoses usually triggered by the antiparkinsonian therapy. One also finds depression and demential syndromes. The appearance of psychiatric complications shows a relation to age, duration, course and stage of the disease, drug dosage and occasionally to situational factors. The pharmacotoxic psychoses, to a certain degree, can be considered as specific for the terminal stages of the disease. They occur in two out of three patients and curtail therapeutic facilities decisively. Depression can not be considered as an integral part of the majority of Morbus Parkinson varieties, since its incidence and severity in old people afflicted with chronic disease, other than parkinson's disease, are not any lower. Dementing processes, in spite of the presently higher average age of the Parkinson population, show a more severe course in other cerebral diseases, like SDAT and MID than in the typical Parkinson patient, free from other cerebral affections. The additional appearance of SDAT and/or MID, with ageing is, however, equally possible.
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PMID:[Psychological changes in Parkinson disease]. 378 91

Modern rehabilitation is becoming more and more "social integration" instead of "going back to work". Therefore rehabilitation is also a matter in chronic disease and in old people. Parkinson patients are somewhat disabled in nearly every aspect of their life, although the extent is related to the stage of the disease. Moreover, symptoms do not respond equally to drug treatment, balance (with succeeding falls) and swallowing being special problems for anti-parkinsonian drug treatment, but also vegetative symptoms, dysarthria, motor skills etc. Apart from medication patients get relief also from adjuvant therapy like physiotherapy, occupational therapy, and speech therapy, which all can lead to improvement of quality of life. Rehabilitation needs team effort. Patient and family supporting groups (like Parkinson Disease Society and others) are an important factor for all needs of neurological rehabilitation.
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PMID:[Parkinson disease and neurologic rehabilitation]. 757 56

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
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PMID:Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. 871 48

The cause of dopamine cell death, thought to be the primary neurocytologic defect in idiopathic Parkinson's disease, remains unknown. Mitochondrial oxidative dysfunction causes premature cell death, and may be linked to accelerated apoptosis, excessive free and toxic radicals, deficient neurotrophic factors or combinations of these detrimental factors. Neurochemical imbalances result both in the substantia nigra and neostriatum, resulting in compensatory mechanisms that make this chronic neurodegenerative disease difficult to evaluate. Acute parkinsonism models have limitations when compared with chronic disease states, and caution should be present when comparing 'parkinsonism' data with human disease. Better understanding of classical neurotransmitters, neuroactive peptides and neurotrophic factors, will hopefully lead to more rational treatment approaches, cellular support strategies, and an understanding of the causes of this disease. Glial derived neurotrophic factor looks the most promising neurotrophic candidate so far tested in culture and in vivo. The result of clinical trials utilizing neurotrophic factors, both as mesencephalic implant support strategies and as definitive treatment of idiopathic Parkinson's disease, are awaited with cautious optimism.
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PMID:Parkinson's disease: biology and aetiology. 885 89

The efficacy of fetal tissue transplants in the treatment of Parkinson's disease has been demonstrated preliminarily. However, results are short term, and have not been confirmed in prospective randomized controlled trials. Furthermore, although patients are improved, they remain severely disabled. There are several problems with the widespread clinical use of fetal tissue that make the use of molecular biological strategies more compelling. Several conceptual problems are shared by both fetal and molecular biological neuroreconstruction strategies. It is necessary to characterize the "dose" of the transplanted therapeutic agent as well as its volume of distribution. The symptoms that may improve following neuronal reconstruction are likely to be directly related to the somatotopic localization of the transplants; the duration of benefit should be long enough to be relevant in a chronic disease such as Parkinson's disease. Operative therapies that utilize gene therapy or other reconstructive neurosurgical techniques are likely to require novel clinical trial designs to demonstrate their efficacy.
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PMID:From transplants to gene therapy for Parkinson's disease. 912 51

There is a renewed interest in sexuality in chronic disease states. Whereas there is some literature on male sexuality in Parkinson's disease (PD), no study has been devoted exclusively to women. We compared 27 women who had PD with community controls matched for age and marital status by using the Brief Index of Sexual Functioning in Women. Approximately 50% of both samples were sexually active. The women with PD were more likely to be dissatisfied with the quality of the sexual experiences. There were significant differences in the two groups with respect to anxiety or inhibition, vaginal tightness, and involuntary urination. Preoccupation with health problems interfering with sex and dissatisfaction with body appearance were also more prevalent in parkinsonian women, but not statistically different from controls. The PD patients were less satisfied with their sexual relationships and with their partners, and were more depressed as a group when compared with controls (Beck Depression Inventory of 11.8 vs 6.3). In both groups, age was associated with significant changes in satisfaction and activity. In summary, qualitative differences exist in the sexual experiences of women with PD compared with controls.
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PMID:Sexuality in women with Parkinson's disease. 939 16

Variability in the relationship between pharmacological effect intensity and drug concentration (pharmacodynamics) is pronounced, usually exceeding pharmacokinetic variability. Whereas interindividual differences are large, intra-individual differences are much smaller, unless the individual experiences certain pathophysiological changes such as deterioration of renal function or progression of a chronic disease (for example, Parkinson's disease). Failure to appreciate the magnitude of interindividual variability in the pharmacodynamics of a drug can compromise fixed dose clinical trial outcomes, making the drug appear less effective or more toxic. In the face of pharmacodynamic variability it becomes important to identify useful predictors (covariates) of pharmacodynamic individuality to facilitate individually optimised pharmacotherapy. This requires clinical trial designs that incorporate extensive patient profiling, well beyond the usual short list of demographics (such as age, gender, race, bodyweight and smoking habits). In searching for predictors, it is helpful to appreciate the factors that may account for interindividual differences in the relationship between pharmacological effect intensity and drug concentration in plasma or other appropriate fluid. They include receptor density and affinity, the formation and elimination kinetics of endogenous ligands (such as the enkephalins), postreceptor transduction processes, homeostatic responses and the kinetic characteristics of transporters involved in drug transfer between fluids of distribution and the biophase. Correction of drug concentrations in plasma for protein binding, consideration of active and interactive metabolites, stereospecific assays and attention to drug distribution disequilibria are essential for successful identification of factors affecting pharmacodynamic variability. Pharmaceutical delivery systems (the 'hardware') must be combined with guidance for individualising drug dosage (the 'software' or user's manual) to provide for optimal and cost-effective pharmacotherapy.
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PMID:Predicting effective drug concentrations for individual patients. Determinants of pharmacodynamic variability. 957 4

The human body is exposed to a wide array of xenobiotics in one s lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning.
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PMID:The detoxification enzyme systems. 963 Jul 36

Sleep disorders are common and well documented in patients with Parkinson's disease (PD). However, most data on sleep in patients with PD are derived from selected patient populations. This community-based survey evaluated the prevalence of and risk factors for sleep disturbances in an unselected group of 245 patients with PD and two control groups of similar age and sex distribution: 100 patients with another chronic disease (diabetes mellitus) and 100 healthy elderly persons. Nearly two thirds of the patients with PD reported sleep disorders, significantly more than among patients with diabetes (46%) and healthy control subjects (33%). About a third of the patients with PD rated their overall nighttime problem as moderate to severe. The most common sleep disorders reported by the patients with PD were frequent awakening (sleep fragmentation) and early awakening. Sleep initiation showed no significant difference compared with the control groups. Pain and cramps were not more prevalent among the patients with PD, but they were more likely to report sleep disturbed by myoclonic jerks. Use of sedatives was common in all three groups but significantly higher in the PD group than in the healthy elderly. Symptoms of depression and duration of levodopa treatment showed a significant correlation with sleep disorders in the PD group. This community-based study confirms that sleep disorders are common and distressing in patients with PD. The strong correlation between depression and sleep disorders in patients with PD underlines the importance of identifying and treating both conditions in these patients.
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PMID:A community-based study of sleep disorders in patients with Parkinson's disease. 982 12


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