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)

Primary care physicians have a vital role to play in identifying depression in their elderly patients. Diagnosis may be difficult, because symptoms are atypical and frequently include psychomotor agitation, somatic symptoms, and complaints of memory loss. Patients with medical illnesses, such as cancer, postmyocardial infarction, stroke, Parkinson's disease, and early Alzheimer's disease are particularly vulnerable to depression. Drugs that may cause depressive symptoms are digitalis at toxic levels, beta-blockers, centrally acting antihypertensives, immunosuppressants, and nonsteroidal anti-inflammatory agents. Cyclic antidepressants are the drugs of first choice. Selection depends on the patient's physical health and current medications and the side effect profile of the drug. Side effects are more pronounced in old age because of drug accumulation owing to slowed clearance. Troublesome side effects are anticholinergic effects, orthostatic hypotension, sedation, cardiotoxicity, and weight gain. The most useful antidepressants for geriatric patients are the secondary amines, desipramine and nortriptyline. The second-generation drug trazodone has the advantage of causing the least anticholinergic effects, but it is very sedating. Before treatment, the patient should have an electrocardiogram, liver function tests, tonometry, sitting and standing blood pressures, evaluation of urinary symptoms for outflow obstruction, review of current medications, and estimation of suicide risk. Cyclic antidepressants are contraindicated during recovery from myocardial infarction, in heart disease when there is severe impairment of myocardial performance, in seizure disorders, and in the presence of glaucoma or a large prostate. Drug interactions that may cause trouble can occur with epinephrine, MAO inhibitors, thyroid hormone, cimetidine, and centrally acting antihypertensives. Dosage should start low, increasing usually by 25 mg every 4 to 5 days until a therapeutic level is reached. Failure of a noradrenergic antidepressant after 4 to 5 weeks can be followed by a trial of a serotonergic drug. Drug serum level monitoring is useful for imipramine, desipramine, and nortriptyline. Monoamine oxidase inhibitors are effective in many elderly patients who are resistant to TCAs. Sympathomimetic drugs must be avoided with MAOIs. Elderly patients are at high risk of toxicity and drug interactions with lithium. Electroconvulsive therapy is useful for patients who do not respond to drug treatment, but medical complications, particularly cardiovascular, often occur in patients 75 or older. Many patients relapse after ECT. Psychotherapy together with pharmacotherapy may be the optimal treatment for elderly depressives. Older patients are more likely to become chronically depressed than younger patients. The risk of suicide in depressed elderly males is high, particularly in those with psychosocial problems, and depression rises with age.
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PMID:Management of depression in the elderly. 266 41

N-0437 is a recently developed dopamine (D2) agonist, theoretically attractive in the therapy of Parkinson's disease and glaucoma. Since its high potency allows small doses of the compound in clinical use and as extensive metabolism occurs in animals, a highly sensitive assay method was required for drug-monitoring purposes. To this end we developed a radioreceptor assay (RRA), a sensitive tool for the assessment of the sample's (dopaminergic) bioactivity. The RRA is based on competition between N-0437 and its tritium-labeled analogue for binding to dopamine receptors. The assay has been optimized for the preparation of the receptor suspension and the incubation conditions. Direct application of the assay for biological samples was impossible because of matrix interferences. Therefore, a solid-phase extraction method was developed in which the combination of a polar Si column and dichloromethane as eluent resulted in an effective elimination of the interferences. Recoveries were better than 90 and 95% for plasma and urine, respectively, even at concentrations at the determination limit of the method (300 pg/ml). Relative standard deviations were less than 15%. Because RRAs are stereoselective, the method discriminates between active and inactive species.
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PMID:Development of a radioreceptor assay for the D2-selective dopamine agonist N-0437. 290 22

To determine which conditions may be associated with reduced survival in patients with Alzheimer's disease, we studied all death certificates in the United States for 1978 on which senile and presenile dementia (ICDA 290, N = 7,195) was mentioned. Each case was compared with two control deaths. Differences in the frequency of listing on the death certificates for the following conditions reached statistical significance: infections, trauma, nutritional deficiency, chronic ulcer of skin, foreign body in pharynx, cataract, glaucoma, blindness, deafness, Parkinson's disease, and epilepsy. There seem to be many preventable and treatable disorders in patients with senile and presenile dementia.
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PMID:Conditions associated with Alzheimer's disease at death: case-control study. 394 92

Visual evoked potential (VEP) abnormality is widely used as an objective indication of visual pathophysiology in the diagnosis of multiple sclerosis. One major limitation of this test is that VEP abnormality is not specific to multiple sclerosis. In an attempt to explore ways of making the VEP test more specific, changes were measured in VEPs caused by superimposing upon the VEP stimulus either a flicker or a moving pattern. The rationale was to test for visual fatigueability, since it is known that some demyelinated axons fatigue rapidly. Of 10 patients with multiple sclerosis, 90% showed VEP fatigue, while none fatigued in the groups of 10 patients with glaucoma and 10 with Parkinson's disease. Fatigue is, however, not completely specific for multiple sclerosis, since three of 10 patients with ocular hypertension showed VEP fatigue.
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PMID:Visual fatigue and visual evoked potentials in multiple sclerosis, glaucoma, ocular hypertension and Parkinson's disease. 608 42

The utility of checkerboard pattern reversal visual evoked potentials in the evaluation of Parkinson disease (Pd) was studied in 25 patients and controls without eye pathology. The results did not reveal differences in potential latency but the amplitude appeared slightly larger in PD than controls. Major intraocular differences were observed only in Pd patients with glaucoma, cataracts or retinal degeneration. The commonly employed high contrast and luminance, checkerboard pattern reversal technique did not appear useful in the evaluation of Pd. Selection of proper stimulus parameters may be critical in detecting VEP abnormality in Pd.
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PMID:Normal checkerboard pattern reversal evoked potentials in parkinsonism. 617 60

Diabetes can cause visual loss that is not detected by standard reading tests such as the Snellen test but can be detected by low-contrast letter charts. This visual loss is quite different from loss caused by refractive error. These low-contrast charts are diagnostically at least as sensitive as the sinewave grating contrast sensitivity test. They are inexpensive, and the test is brief and simple. Preliminary evidence is that patients with diabetes who have abnormal low-contrast chart results give abnormal intravenous fluorescein (IVF) test results, even though visual acuity is normal. Low-contrast charts also detect visual loss in patients with ocular hypertension, glaucoma, and Parkinson's disease, including patients with normal visual acuity.
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PMID:Low-contrast letter charts in early diabetic retinopathy, ocular hypertension, glaucoma, and Parkinson's disease. 650 9

In the Rotterdam Study, prevalence and determinants of chronic diseases in the elderly (age > or = 55 years), were investigated in inhabitants of Ommoord, a suburb of Rotterdam. The study focused on cardiac diseases (myocardial infarction, angina pectoris, cardiovascular risk factors), glaucoma, macular degeneration, osteoporosis, osteoarthrosis and invalidity, dementia (Alzheimer's disease, vascular dementia, Parkinson's disease), epilepsy, cerebrovascular accident. The number of participants was 7983 (3105 men, 4878 women), a response of 78%. The participants were interviewed and were twice examined in an out-patient clinic. The results will be described in subsequent issues of this journal.
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PMID:[Prevalence of chronic diseases in the elderly; the ERGO study (Erasmus Rotterdam Health and the Elderly)]. 747 40

1. Due to their involvement in the termination of neurotransmission at cholinergic synapses and neuromuscular junctions, cholinesterases are the target proteins for numerous drugs of neuro-psychopharmacology importance. 2. In order to perform structure-function relationship studies on human cholinesterases with respect to such drugs, a set of expression vectors was engineered, all of which include cloned cDNA inserts encoding various forms of human acetyl- and butyrylcholinesterase. These vectors were designed to be transcribed in vitro into their corresponding mRNA products which, when microinjected into Xenopus oocytes, are efficiently translated to yield their catalytically active enzymes, each with its distinct substrate specificity and sensitivity to selective inhibitors. 3. A fully automated microtiter plate assay for evaluating the inhibition of said enzymes by tested cholinergic drugs and/or poisons has been developed, in conjunction with computerized data analysis, which offers prediction of such inhibition data on the authentic human enzymes and their natural or mutagenized variants. 4. Thus, it was found that asp70-->gly substitution renders butyrylcholinesterase succinylcholine insensitive and resistant to oxime reactivation while ser 425-->Pro with gly70 gives rise to the "atypical" butyrylcholinesterase phenotype, abolishing dibucaine binding. 5. Furthermore, differences in cholinesterase affinities to physostigmine, ecothiophate and bambuterol were shown in these natural variants. 6. Definition of key residues important for drug interactions may initiate rational design of more specific cholinesterase inhibitors, with fewer side effects. This, in turn, offers therapeutic potential in the treatment of clinical syndromes such as Alzheimer's and Parkinson's disease, glaucoma and myasthenia gravis.
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PMID:Structure-function relationship studies in human cholinesterases reveal genomic origins for individual variations in cholinergic drug responses. 827 1

The aim of this study was to identify characteristics that predispose older residents of Adelaide to falling. Information collected in the baseline phase of the Australian Longitudinal Study of Ageing was used to draw cross-sectional comparisons between participants who reported having fallen on at least one occasion in the previous 12 months and those participants who reported not having fallen. The baseline cohort consisted of 1947 participants aged 70 years or more, of whom 550 (28 per cent) reported having fallen at least once in the previous year. Independent risk factors for falling were: age; having left school at an early age; a worsening of vision in recent years; and histories of Parkinson's disease, fractured hip, glaucoma, stroke (including transient ischaemic attack), corns or bunions, or arthritis. The findings regarding medical histories suggest some possible opportunities for reducing the risk of falls in the elderly by managing the symptoms and risk factors of underlying conditions such as stroke and loss of vision.
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PMID:Factors associated with falling in older Adelaide residents. 934 89

A follow-up study was conducted among men and women aged 55 years and over living in the community in order to estimate the incidence of initiation of antidepressant drug use and the association with chronic diseases. The study population consisted of 7,812 individuals. Overall, the incidence density for starting therapy with an antidepressant drug was 13.5 per 1000 person-years. The cumulative incidences after 1, 2 and 3 years were 1.3, 2.7 and 4.0%, respectively. The incidence in women was almost twice that in men and slightly higher in participants older than 70 years than in those younger than 70 years. The majority of the antidepressants prescribed were tricyclic antidepressants (65%), followed by selective serotonin reuptake inhibitors (23%) and other (12%) antidepressants. Only a minority (23%) received a dose considered effective for the indication of depression. Selective serotonin reuptake inhibitors were more often prescribed in an adequate dosage (68%) than were tricyclic antidepressants (12%) and other antidepressants (8%). Of the chronic diseases studied, only osteoarthritis and a history of stroke were predictors of initiation of antidepressant drug use after adjustment for age, sex and medical consumption. Hypertension, history of myocardial infarction, diabetes mellitus, rheumatoid arthritis, glaucoma, cognitive impairment and Parkinson's disease were not associated with future antidepressant drug use. No relevant differences were observed with respect to the choice of type of antidepressant drug among patients with chronic diseases. The present study indicates that each year antidepressant drug therapy is initiated in approximately 1.3% of the elderly. In general, the presence of chronic somatic diseases was not predictive of initiation of antidepressant drugs. Tricyclic antidepressants in this age group and in patients with certain chronic diseases may not be the optimal choice given their side-effects profile and drug-drug and drug-disease interactions. The predominance of these agents in the present study calls for further attention.
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PMID:Incidence of antidepressant drug use in older adults and association with chronic diseases: the Rotterdam Study. 934 83


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