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)

Selection bias may be introduced in case-control or cross-sectional studies, and the impact on the observed associations may be dramatic. Many authors have examined this issue primarily in the context of subject source (e.g. referral bias). The potential bias encountered when a risk factor associated with outcome is also associated with an increase in mortality among cases greater than that among those not developing the disease (e.g. selective survival) is examined here. The potential for selective survival bias arising in observational studies is demonstrated in studies of the etiology of neonatal seizures and Parkinson's disease.
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PMID:Differential postmorbidity mortality in observational studies of risk factors for neurologic disorders. 796 1

Risk factors of Parkinson's disease (PD) were studied by the case-control method (1:1) in 90 cases. It was suggested that the high positive rate (34.4%) in PD family history was related to "genetic susceptibility". There was history of head injury, rheumatic fever, seizure, taking anti-psychosis drug or contact with toxins, but any one factor could not completely explain the etiology of PD. We believe that coordinating effects of both susceptibility in genetics and environmental toxins may explain the mechanism of PD.
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PMID:[A case-control study on risk factors in etiology of Parkinson's disease]. 808 43

We report the findings of a total population survey of Thugbah community in the Eastern Province of Saudi Arabia (SA) to determine its point prevalence of neurological diseases. During this two-phase door-to-door study, all Saudi nationals living in Thugbah were first screened by trained interviewers using a pretested questionnaire (sensitivity 98%, specificity 89%) administered at a face-to-face interview. Individuals with abnormal responses were then evaluated by a neurologist using specific guidelines and defined diagnostic criteria to document neurological disease. The questionnaire was readministered blind by a neurologist to all those with abnormal responses and a 1-in-20 random sample of those without abnormal responses, respectively. The family members of an individual with an abnormal response were also screened to improve accuracy. A total of 23,227 Saudis (98% of the eligible subjects) were screened and those residing in Thugbah on the reference date (22,630) were used to calculate the point prevalence rates. Forty-two percent of those screened were in the first decade of life and only 1.5% were more than 60 years old. There were marginally more females (50.2%) than males (49.8%). Consanguineous marriages especially between first cousins were present in 54.6%. The demographic characteristics of Thugbah community were similar to those in other parts of SA. The overall crude prevalence ratio (PR) for all forms of neurological disease was 131/1,000 population. All subsequent PRs are per 1,000 population. Headache syndromes were the most prevalent disorder (PR 20.7). The PR for all seizure disorders was 7.60, and the epilepsies (6.54) were more frequent than febrile convulsions (0.84). Mental retardation, cerebral palsy syndrome, and microcephaly were common pediatric problems with PRs of 6.27, 5.30 and 1.99, respectively. Stroke, Parkinson's disease, and Alzheimer's disease were uncommon with respective PRs of 1.8, 0.27 and 0.22. Central nervous system (CNS) malformations (0.49) such as hydrocephalus and meningomyelocele were more prevalent than spinal muscular atrophy (0.13), congenital brachial palsy (0.13) and narcolepsy (0.04). Multiple sclerosis was rare (0.04). Osteoarthritis and low back pain syndromes were the main non-neurological conditions seen. The major medical diseases that may be neurologically relevant were diabetes mellitus, hypertension, and connective tissue disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A community survey of neurological disorders in Saudi Arabia: the Thugbah study. 827 77

Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 microM suggesting that budopine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).
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PMID:The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist. 833 6

The first disease due to disturbances in a cell organelle was discovered in 1959-62, and its basis was loose-coupling of oxidative phosphorylation in the skeletal muscle mitochondria accompanied by severe alterations of their structure (Luft's disease). During the 1980s, functional disturbances and structural alterations in the mitochondria were observed in more than 100 disease entities, mainly in parts of the central nervous system and skeletal muscles. A second breakthrough in this area was the discovery in 1963-64 that mitochondria had their own DNA, mtDNA. Following the observation in 1988 of mutations of mtDNA in mitochondrial diseases, such mutations--mainly deletions and point mutations--were observed in almost all mitochondrial diseases. A remarkable extension of the area is the notion that "normal" ageing is accompanied by decreased oxidative phosphorylation and the appearance of mtDNA mutations. During the last two years, such changes have been demonstrated in diseased states in tissues and organs, which are especially reliant on oxygen supply: in the central nervous system (Parkinson's disease, some types of epilepsy and seizures, Huntington's disease, possibly also in Alzheimer's disease); in heart muscle (cardiomyopathies) and in skeletal muscle. Type 2 diabetes or NIDDM engages two tissues most reliant on oxygen consumption, the pancreatic islets (insulin secretion) and skeletal muscle (insulin sensitivity). Both these functions are genetically determined, the latter to a high degree also controlled by "environmental" factors. The evident age factor in the development of NIDDM could be on a par with the "normal" ageing process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Physiopathology of mitochondria. From Luft's disease to aging and diabetes]. 836 14

Epilepsy means are frequent neurologic disorders caused by abnormal electric cerebral discharges of diverse origins. While most epileptic patients experience satisfactory suppression of seizures by drug regimens, a substantial number requires a neurosurgical intervention for improvement. This is particularly the case with epilepsy originating from the temporal lobe. 35 interventions for seizure disorders are actually carried out in Zurich each year. For the whole of Switzerland this could, depending on the criteria for an indication, mean from 150 to 1500 annual intervention. In any case an accurate localization of the epileptic focus is a prerequisite. Over the past years it has been shown that such foci and their surrounding exhibit often an abnormal pattern of glucose utilisation, which can be visualized by PET. In various centers for epileptic disorders worldwide, invasive preoperative neurophysiologic investigations are no longer used in view of these results. In extrapyramidal disorders (i.e. Parkinson's disease or Huntington's chorea), disturbances of basal ganglia occur. PET studies of these areas center around measurements of glucose metabolism, synthesis of dopamine and dopaminergic receptors. Such studies provide new insight into the pathophysiology of these diseases. They provide diagnostic clues in difficult cases and permit assessment of extent and progression of degeneration. Functional PET measurements also open new avenues for clinical pharmacology.
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PMID:[Positron-emission tomography (PET) in epilepsy and extrapyramidal disorders]. 837 95

For those conditions in which loss of consciousness is the main issue, such as epilepsy, factors that contribute to risk of seizure recurrence are central to the determination of driver safety. Thus, high- and low-risk groups may be identified and factors that contribute to high risk checked. These factors also serve to develop a program to reduce such risk in the future. In the population with seizure disorders, young males under age 25 have the highest risk for traffic accidents and violations. Other factors associated with high risk are partial complex seizure type, history of drug toxicity with anticonvulsant medications, alcohol abuse or poor compliance for medications, and history of psychiatric illness. For conditions such as cerebrovascular accidents or Parkinson's disease, the recognition of the diagnosis alone is insufficient to determine driver competence. In these illnesses, the task is to recognize levels of failure of individual skills and function that specifically render a person incompetent for safe driving. Such a precise determination is currently not possible in individuals with cerebrovascular accidents or other forms of brain injury (e.g., trauma) or degenerative brain disease (e.g., Parkinson's disease). There is intuitive and general agreement that there are those so severely affected that driving has become impossible or very dangerous. Alternately, there are also those with these conditions whose driving skills and competence are virtually unaffected and pose no risk to traffic safety. Physicians vary widely in their ability and experience in judging the competence and safety of those in between these two extremes. For this reason, a standardized approach is essential both to ensure the avoidance of unnecessary bias as well as to ensure the safety of the driver and the general public. At some time in the future when all the necessary driving skills are identified and appropriate tests are developed to judge them, a battery of tests for the elderly at age 65 and at regular intervals thereafter may be used. Until then, some form of clinical judgment and legal regulation may have to be adopted. One option would be to adopt a rule similar to that in the United Kingdom where all persons with TIAs or cerebrovascular accidents would automatically suspend driving for 3 months because of the high risk for recurrence of both cerebrovascular as well as ischemic heart disease in that interval.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Seizure disorders, diabetes mellitus, and cerebrovascular disease. Considerations for older drivers. 850 82

A retrospective analysis of 812 patients admitted to the Ross Tilley Burn Centre between 1984 and 1992 resulted in 37 cases of burn injuries which were directly related to premorbid disabilities. The majority of these burns (83.8 per cent) occurred in the patient's home, most commonly as scald injuries in the bath tub, the shower, or following hot water spills. Nineteen patients were male, 17 were female. The median age was 58 years. Six patients had spinal cord disorders: four had traumatic cord damage, two had spina bifida. Six patients had seizure disorders. Five of these patients had been taking anti-seizure medications, but all had subtherapeutic blood levels on admission to hospital. Two patients had diabetes mellitus with peripheral neuropathies. Thirteen patients had four miscellaneous neurological disorders, including: tardive dyskinesia (two), CVA (four), Parkinson's disease (two), Alzheimer's disease (two), cerebral palsy (one), multiple sclerosis (one) and blindness (one). Three patients had a diagnosis of syncope. Two patients had emphysema, and four were morbidly obese. The average length of stay (LOS) for the disabled patients was 27.6 days for a median burn size of 10 per cent body surface area (BSA), compared to an average LOS for the general population of 25.7 days for a larger median burn size of 21 per cent BSA. The mortality rate was also much higher in the disabled population (22.2 per cent vs. 6.0 per cent). Most of these burn injuries were preventable. A series of burn prevention guidelines is presented, in an attempt to reduce the incidence of these burn injuries in disabled patients.
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PMID:Burns in the disabled. 850 62

The amino-adamantane derivatives memantine (1-amino-3,5-dimethyladamantane) and amantadine (1-amino-adamantane) are relatively low affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists which have been used clinically in the treatment of dementia and Parkinson's disease respectively for several years without serious side effects. The aim of this study was to test whether memantine, amantadine and other low affinity uncompetitive NMDA receptor antagonists also have better therapeutic indices than high affinity antagonists in preclinical models of epilepsy by assessing the potency, kinetics and voltage-dependency of open channel blockade for a series antagonists in vitro and comparing these effects to anticonvulsive and motor impairment activity in vivo. The compounds tested were memantine, amantadine, 14 other amino-adamantanes, (+)-MK-801, ketamine, dextrorphan, dextromethorphan and phencyclidine. The offset kinetics of open-channel blockade assessed with whole cell patch clamp recordings from cultured superior colliculus neurones were highly correlated to potency i.e. the less potent antagonists showed faster unblocking kinetics (Koff, r = 0.904). Although, onset kinetics as assessed by Kon were not correlated to potency (r = 0.023), tau on estimated at IC50 is perhaps a more meaningful measure of onset kinetics at equieffective concentrations and was also well correlated to potency (r = -0.863). All amino-adamantanes tested were strongly voltage-dependent. There was also a good correlation between the in vitro potencies of uncompetitive NMDA receptor antagonists assessed with patch clamp recordings and displacement of equilibrium [3H](+)-MK-801 binding and their in vivo activity against maximal electroshock (MES) and pentylenetetrazol (PTZ) induced tonic convulsions and NMDA-induced lethality in mice. Memantine and four other amino-adamantanes with somewhat lower potency and faster blocking kinetics had better therapeutic indices (ED50 rotarod and traction reflex over ED50 in MES-induced convulsions; TI = 2-4) than substances with higher affinity such as ketamine, dextrorphan and (+)-MK-801 (TI < 2). However, amantadine and several other amino-adamantanes with lower potency than memantine actually had poorer therapeutic indices (TI < or = 0.5) which may have been due to additional actions at other ion channels or receptors at the doses necessary to protect against seizures. In fact, ED50 in the MES test was negatively-correlated to therapeutic indices (traction r = -0.790, rotarod r = -0.797) i.e. the less potent uncompetitive antagonists had worse therapeutic indices. The data from the present study do not lend support to the idea that low affinity, open channel NMDA receptor blockers are also effective in models of epilepsy at doses having little effect on physiological processes. It should be stressed that these data do not contradict the known therapeutic safety of memantine and amantadine in dementia and Parkinson's disease respectively. Thus the good clinical profile of memantine in dementia has been attributed not only to its fast blocking/unblocking kinetics but also to its strong voltage-dependency. These biophysical properties may allow therapeutically-relevant concentrations to block chronic, low level pathological activation of NMDA receptors whilst leaving their synaptic activation intact. Precisely these properties may also underlie the poor therapeutic indices seen in the present study on antiepileptic activity due to the synaptic nature of both seizures and normal glutamatergic transmission.
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PMID:Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. 857 22

The paradox of aerobic life, or the 'Oxygen Paradox', is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This 'dark side' of oxygen relates directly to the fact that each oxygen atom has one unpaired electron in its outer valence shell, and molecular oxygen has two unpaired electrons. Thus atomic oxygen is a free radical and molecular oxygen is a (free) bi-radical. Concerted tetravalent reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the univalent reduction of oxygen generates reactive intermediates. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled univalent reduction. Thus the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate--or garner from their surroundings--a variety of water- and lipid-soluble antioxidant compounds. Additionally, a series of antioxidant enzymes, whose role is to intercept and inactivate reactive oxygen intermediates, is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxidant drugs and foods. Alternatively, compounds found in certain foods may be able to significantly bolster biological resistance against oxidants. Currently, great interest centres on the possible protective value of a wide variety of plant-derived antioxidant compounds, particularly those from fruits and vegetables.
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PMID:Oxidative stress: the paradox of aerobic life. 866 Mar 87


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