Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the focal therapeutic effect of oily carcinostatic agents administered by transcatheter arterial infusion (TAI) as the initial therapy in patients with hepatocellular carcinoma in a randomized controlled clinical trial. Group A (19 patients) received 4 mg of styrene maleic acid neocarzinostatin in 4 ml of Lipiodol, and group B (18 patients) received 100 mg of epirubicin in 4 ml of Lipiodol via the tumor feeding arteries as peripherally as possible. The grade of Lipiodol accumulation and the tumor regression rate were determined 2 weeks after TAI by computerized tomography. Adverse effects within 2 weeks after TAI were evaluated by subjective signs and symptoms such as fever (maximum body temperature) and the frequency of shaking chills and abdominal pain, and by biochemical parameters such as albumin, prothrombin time, and aspartate and alanine aminotransferases. Lipiodol accumulation in the tumor was significantly greater in group A (12/19; 63.2% showing grade IV Lipiodol accumulation) than in group B (3/18; 16.7% showing grade IV) (P<0.05). The tumor regression rate was also significantly greater in group A (8/17; 47.1% showing more than 25% tumor regression) than in group B (1/13; 7.7% showing more than 25% tumor regression) (P<0.05). Although clinically significant elevations of aminotransferases and reductions of cholinesterase, and shaking chills were observed more often in group A than in group B (P<0.0001), these factors had little influence on the clinical outcome. Our results suggest that styrene maleic acid neocarzinostatin in Lipiodol exerts a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of hepatocellular carcinoma.
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PMID:Focal therapeutic efficacy of transcatheter arterial infusion of styrene maleic acid neocarzinostatin for hepatocellular carcinoma. 1063 37

Young rats have been shown in several laboratories to be more sensitive to the neurotoxic effects of acute exposure to chlorpyrifos. To examine the neurobehavioral effects of chlorpyrifos as a function of age and dose, we conducted dose-response and time-course assessments in rats of three different ages (postnatal day, or PND, 17, 27, and adults). Doses were selected to span the effective dose range in each age group: PND17 - 4, 10, 20 mg/kg; PND27 - 10, 25, 50 mg/kg; adult - 10, 50, 100 mg/kg. Rats were tested at the time of peak effect on the day of dosing, and again at 1 and 3 days, and at 1 and 2 weeks after a single oral dose. There were age- and sex-related differences in the recovery of these behavioral effects; the adult males recovered from the behavioral effects more quickly than the other age groups, and the adult females showed the slowest recovery (up to at least 3 days). Although these doses had been shown previously to produce a similar degree of cholinesterase inhibition, the neurobehavioral alterations fell into the following three patterns of effect as a function of age. (1) Some endpoints (e.g., gait abnormalities, tremor) showed a dose-response curve that was shifted to the right in the older animals. Calculated ED50 values indicated that the PND17 rats were three- to five-fold more sensitive than the adults. (2) Some measures showed less effect in the youngest rats; for example, maximal motor activity decreases were half as great as with adults. (3) A few effects that were typically observed in adults, e.g., salivation, were not seen at all in the PND17 rats. Thus, differential responses on these neurobehavioral endpoints were observed as a function of age. These data suggest that, for some endpoints, young rats are more sensitive to a range of chlorpyrifos doses; however, the magnitude of age-related differences depends on the specific endpoint and time of assessment, as well as age and sex of the test subject.
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PMID:Dose-response and time-course of neurobehavioral changes following oral chlorpyrifos in rats of different ages. 1110 64

We present a 73-year-old man with probable dementia with Lewy bodies(DLB). At 65 years of age, he gradually developed bradykinesia, gait disturbance and mild amnesia. At 71 years of age, he noted resting tremor in bilateral hands, and amnesia and disorientation were exacerbated. He was diagnosed as having parkinsonism and took L-dopa/carbidopa at 100 mg/day. Since he developed hallucination and abnormal behavior 2 days after the initiation of the drug, he stopped taking L-dopa and was admitted to our hospital. A neurological examination on admission revealed moderate amnesia, disorientation, finger agnosia, constitutional apraxia, mask-like face, cogwheel rigidity, resting tremor in bilateral hands, and bradykinesia. Brain MRI showed mild brain atrophy, and single photon emission computerized tomography(SPECT) showed diffuse moderate hypoperfusion in bilateral cerebral cortex. As he had fluctuating cognitive dysfunction and parkinsonism, he was diagnosed to have probable DLB. As his dementia was exacerbated by trihexyphenidyl, an anti-cholinergic agent, at 2 mg/day, we treated him with donepezil, an anti-choline esterase agent, at 3-5 mg/day. His parkinsonism, including rigidity and bradykinesia, was markedly improved his dementia, consisting of amnesia and disorientation. Electroencephalography (EEG) improved in the organization of the dominant rhythm. The SPECT improved in the blood perfusion of the bilateral frontal lobe as well as cognitive function and parkinsonism were maintained by donepezil for 6 months after discharge. A therapeutic efficacy of donepezil for DLB has recently been reported. It is notable that donepezil was beneficial not only for cognitive dysfunction but also for parkinsonism in the present case with probable DLB.
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PMID:[A patient with probable dementia with Lewy bodies, who showed improvement of dementia and parkinsonism by the administratim of donepezil]. 1180 50

Specimens of medaka (Oryzias latipes) were observed continuously through an automatic image recognition system before and after treatments of an anti-cholinesterase insecticide, diazinon (0.1 mg/l), for 4 days in semi-natural conditions (2 days before treatment and 2 days after treatment). The "smooth" pattern was typically shown as a normal movement behavior, while the "shaking" pattern was frequently observed after treatments of diazinon. These smooth and shaking patterns were selected for training with an artificial neural network. Parameters characterizing the movement tracks, such as speed, degree of backward movements, stop duration, turning rate, meander, and maximum distance movements in the y-axis of 1-min duration, were given as input (six nodes) to a multi-layer perceptron with the back propagation algorithm. Binary information for the smooth and shaking patterns was separately given as the matching output (one node), while eight nodes were assigned to a single hidden layer. As new input data were given to the trained network, it was possible to recognize the smooth and shaking patterns of the new input data. Average recognition rates of the smooth pattern decreased significantly while those for the shaking pattern increased to a higher degree after treatments of diazinon. The trained network was able to reveal the difference in the shaking pattern in different light phases before treatments of diazinon. This study demonstrated that artificial neural networks could be useful for detecting the presence of toxic chemicals in the environment by serving as in-situ behavioral monitoring tools.
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PMID:Pattern recognition of the movement tracks of medaka (Oryzias latipes) in response to sub-lethal treatments of an insecticide by using artificial neural networks. 1244 90

Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic neurotransmission. Overstimulation of cholinergic receptors by excess acetylcholine is known to be lethal. However, AChE knockout mice live to adulthood, although they have weak muscles, do not eat solid food, and die early from seizures. We wanted to know what compensatory factors allowed these mice to survive. We had previously shown that their butyrylcholinesterase activity was normal and had not increased. In this report, we tested the hypothesis that AChE-/- mice adapted to the absence of AChE by downregulating cholinergic receptors. Receptor downregulation is expected to reduce sensitivity to agonists and to increase sensitivity to antagonists. Physiological response to the muscarinic agonists, oxotremorine (OXO) and pilocarpine, showed that AChE-/- mice were resistant to OXO-induced hypothermia, tremor, salivation, and analgesia, and to pilocarpine-induced seizures. AChE+/- mice had an intermediate response. The muscarinic receptor binding sites measured with [3H]quinuclinyl benzilate, as well as the protein levels of M1, M2, and M4 receptors measured with specific antibodies on Western blots, were reduced to be approximately 50% in AChE-/- brain. However, mRNA levels for muscarinic receptors were unchanged. These results indicate that one adaptation to the absence of AChE is downregulation of muscarinic receptors, thus reducing response to cholinergic stimulation.
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PMID:Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice. 1266 13

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.
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PMID:Treatment of psychosis in Parkinson's disease: safety considerations. 1281 32

The effects of four organophosphorous compounds, three oximes and atropine sulphate, injected through an indwelling cannula into the third ventricle of unanaesthetized dogs were examined. The effects of 200 mug of dyflos were involuntary micturition, defaecation, akinesia of hind limbs and pronounced disturbances of awareness; those of 100 mug of ethyl pyrophosphate were tremor, restlessness and signs of fear; 500 mug to 5 mg of dyflos and 250 mug to 500 mug of ethyl pyrophosphate caused vomiting, salivation, twitches of facial muscles and recurrent epileptiform seizures. The injection of 40 to 80 mg of dimefox and of 50 mg of schradan elicited involuntary micturition, vomiting, salivation and defaecation. These effects occur probably after these substances have passed into the blood stream and have been converted in the liver to potent anticholinesterases. This view is supported by the finding of reduced blood cholinesterase activity. At a dose level of 12.5 mg, 1,1'-trimethylenebis(4-hydroxyiminomethylpyridinium bromide) produced strong convulsions. At this dose level pralidoxime iodide and diacetyl monoxime produced no observable effects. Atropine sulphate in a dose of 1 mg caused disturbances in consciousness and behaviour followed by convulsions. Intraventricular atropine and to a minor extent intraventricular oximes were able to antagonize the effects of intraventricular ethyl pyrophosphate. Pralidoxime iodide exerted a strong antagonistic effect also on intravenous injection.
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PMID:Effects of organophosphorous compounds, oximes and atropine injected into the third ventricle of unanaesthetized dogs. 1388 82

Cholinesterase inhibitors vary in their selectivity for acetylcholinesterase versus butyrylcholinesterase. We examined several cholinesterase inhibitors and assessed the relative role of acetylcholinesterase versus butyrylcholinesterase inhibition in central and peripheral responses to these medications. Donepezil and icopezil are highly selective for acetylcholinesterase, whereas tacrine and heptylphysostigmine demonstrated greater potency for butyrylcholinesterase over acetylcholinesterase. All four compounds increased acetylcholine levels in mouse brains. Dose-response curves for tremor (central effect) and salivation (peripheral effect) showed that donepezil and icopezil possess a more favourable therapeutic index than the nonselective inhibitors, tacrine and heptylphysostigmine. Co-administration of the selective butyrylcholinesterase inhibitor tetraisopropylpyrophosphoramide (iso-OMPA) potentiated peripheral, but not central, effects of the selective acetylcholinesterase inhibitor icopezil. The improved therapeutic index observed in mice with icopezil is due to a high degree of selectivity for acetylcholinesterase versus butyrylcholinesterase, suggesting that high selectivity for acetylcholinesterase may contribute to the clinically favourable tolerability profile of agents such as donepezil in Alzheimer's disease patients.
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PMID:Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer's disease. 1475 2

Parkinson's disease (PD) is a chronic neurodegenerative disease, in which mainly dopaminergic neurons in the substantia nigra in the brain degenerate, leading to a depletion of dopamine (DA) in the striatum. The most important motor disturbances of the disease are bradykinesia (slowing down of movement), hypokinesia (poverty of movement), rigidity (muscle stiffness), tremor and postural instability. Besides these well-known motor symptoms, non-motor symptoms may develop, such as depression, cognitive impairment and psychosis. Psychotic symptoms constitute a relatively common but nevertheless serious complication, with visual hallucinations and paranoid delusions often being most prominent. These symptoms are important contributors to patient and caregiver distress and are often important risk factors for nursing home placement. Exogenous (related to therapeutic interventions) factors are of major importance but endogenous (related to the disease process itself) factors might also contribute to the development of psychotic symptoms in PD. Therapeutic strategies comprise reduction of antiparkinsonian treatment, cholinesterase inhibitors and atypical antipsychotics. As psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of strategies may be chosen.
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PMID:Psychotic symptoms in Parkinson's disease: pathophysiology and management. 1515 49

We describe 4 cases of delayed extrapyramidal disorder following acute dichlorvos poisonings. All patients were seriously poisoned since all exhibited profound coma and respiratory failure, and they were all tracheally intubated and mechanically ventilated. On admission, plasma cholinesterase activity was greaty decreased, < 10 micromol/ml/h at 37 C in all patients (< 10% of normal for our laboratory). Extrapyramidal symptoms occurred between 5 and 15 d and were characterized by dystonia of arms and legs, resting tremor, cogwheel rigidity, and hypereflexia. With bromocriptine therapy the features of extrapyramidal syndrome disappeared progressively with complete recovery in all patients. Our observations suggest a delayed extrapyramidal syndrome should be taken into account during the course of acute dichlorvos organophosphate poisonings.
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PMID:Extrapyramidal syndrome as a delayed and reversible complication of acute dichlorvos organophosphate poisoning. 1530 89


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