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)

Extrapyramidal signs (EPS) were compared in 98 dementia with Lewy bodies (DLB) and 130 medication-responsive Parkinson's disease (PD) patients. DLB patients were older at assessment and at disease onset, were cognitively more impaired, and had a shorter duration of disease than PD patients. Sixty-seven DLB patients (68%) showed EPS. The 58 DLB patients with complete data had more severe action tremor, body bradykinesia, difficulty arising from a chair, and facial expression, gait, and rigidity symptoms than PD patients (all P<0.001). Abnormal posture and tremor at rest did not differ. Severity of EPS correlated with age, duration of disease, and cognitive impairment in PD patients but not in DLB patients. Studies of the clinical significance and management of EPS in DLB patients are needed.
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PMID:Comparison of extrapyramidal signs in dementia with Lewy bodies and Parkinson's disease. 1151 44

The objective of this study was to define risk factors for depression in patients with idiopathic Parkinson's disease (PD) and to evaluate the correlation of depression with cognitive function and the primary domains of parkinsonian motor dysfunction tremor, bradykinesia, rigidity, gait and balance impairment. The risk factors for depression in patients with PD remain controversial. Several investigators have demonstrated a significant association between cognitive dysfunction and depression, but motoric and disease variables can confound this evaluation and have shown an inconsistent relation to depression. A consecutive series of 88 patients with PD were examined using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRSm), Hoehn-Yahr stage (HY), and Hamilton Rating Scale for Depression (HRSD). Major depression was diagnosed according to the criteria in the Diagnostic and Statistic Manual of Mental Disorders, 4th edition. Gender, age, handedness, PD duration, side of PD onset, motor fluctuations, UPDRSm total score, daily Levodopa dose, and Mini-Mental State Examination score (MMSE) were analyzed using multivariate and univariate logistic regression, Fisher's Exact test, and Pearson correlations. Major depression was diagnosed in 12 patients (7.3%). Low MMSE score, axial bradykinesia, gait and balance impairment were strongly significant predictors of depression. In conclusion, depression and physical function are important factors impairing the quality of life for patients with PD, and regular depression screening and treatment should focus on patients with PD who have cognitive impairment, high axial bradykinesia, gait and balance impairment.
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PMID:Cognitive and motor function in patients with Parkinson's disease with and without depression. 1157 67

Direct and indirect signs and symptoms of Parkinson's disease are a major cause of disability in the elderly. Intrinsic symptoms comprise not only the well-known clinical hallmarks of this disease with motor behavioral abnormalities, such as bradykinesia, hypokinesia, rigidity and tremor, but also autonomic failure with orthostatic hypotension, urinal incontinence and impotence as well as non-motor behavioral abnormalities: mental dysfunction characterized by mood disorders, cognitive dysfunction and, sporadically, delusions and hallucinations. These symptoms are caused by a progressive abnormal degeneration of the dopamine (DA) producing cells in the substantia nigra (SN) and ventral tegmentum area (VTA) in combination with an interindividual fluctuating degree of decay in the noradrenergic (locus coeruleus), cholinergic forebrain (nucleus basalis of Meynert) and serotoninergic (dorsal raphe nuclei) systems. Extrinsic symptoms, induced by pharmacotherapy, mainly manifest with (un)predictable motor response fluctuations and dopaminomimetic psychosis. Psychological and psychiatric symptoms in Parkinson's disease (PD) are important predictors of the patient's quality of life. As these symptoms are potentially treatable, identification is of major clinical importance both for the patients and their caregivers and may enable to maintain Parkinson's disease patients at home for a longer period.
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PMID:Intrinsic and extrinsic psychosis in Parkinson's disease. 1169 84

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32-50 years of age (mean +/- SD, 39.7 +/- 7.6 years) and they had a mean disease duration of 5.4 +/- 2.1 years (range, 2-9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.
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PMID:Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation. 1221 Aug 94

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

Although all dopaminergic drugs are effective in reducing tremor, no single drug has been shown to be clearly superior in the treatment of tremor. Levodopa produces a mean improvement of 30 to 50% in the Unified Parkinson's Disease Rating Scale (UPDRS) subtest for rest tremor. Comparable improvement is achieved with the dopamine agonists. Dopamine agonists are particularly well suited for patients with newly diagnosed tremor-predominant disease and no cognitive impairment, but they are also useful in advanced patients with tremor that is refractory to levodopa and anticholinergics. The response of tremor to pharmacotherapy is variable, and clinicians must be prepared to try all of the available drugs before concluding that surgery is the only alternative.
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PMID:Tremor and dopamine agonists. 1190 86

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable.
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PMID:Treatment results: Parkinson's disease. 1194 59

There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.
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PMID:Cannabinoid receptors and their ligands. 1205 30

The cognitive (executive) ability of patients with Parkinson's-disease (PD) deteriorates gradually during the progression of the disease. Fluency of speech, word finding, working memory, ability to plan the future and flexibility decline. Cognitive disturbance was found to be proportional with the speech, posture, gait and balance problems and can not be influenced by L-dopa substitution. Apart the dorsal and ventral mesolimbic dopaminergic systems the coerulo-cortical noradrenergic, serotoninergic and cholinergic systems are also impaired in PD. Subcortical dementia in PD can also be explained by the functional disability of dorsolateral and anterior cingular circuits. Attention deficit can be explained by the dopamine depletion of cingular cortex. Cortical Lewy bodies, neurofibrillary tangles, neurit plaques and additional vascular pathology should also play a role in cognitive impairment of PD. In several systemic degenerative diseases associating with Parkinson's syndrome (PS) i.e. progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA) dementia can be detected with various severity, therefore the question arises concerning the correlation between cognitive disability and PS. Parkinson syndrome can also develop in frontotemporal dementias (FTD), Alzheimer's disease and cortical Lewy body disease (CLBD) but no correlation exists between motor disability and severity of dementia. In CLBD dementia can be the initial symptom in 18% of cases but PS can also preceeds the dementia. In PSP profound depletion of other monoaminergic neurotransmitter system was also reported. In FTDs associated with PS degeneration of substantia nigra, locus coeruleus and basal nucleus of Meynert has been reported with increased number of neurofibrillary tangles. In patients with vascular PS (VP) there is generally no tremor and rigidity, but pseudobulbar palsy, dementia, gate disturbance, incontinency appears; L-dopa treatment is generally ineffective. In VP no cellular loss can be found within the substantia nigra, but leukoaraiosis, lacunae in the white matter and basal ganglia are commonly demonstrated.
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PMID:[Parkinson syndrome and cognitive disorders]. 1220 Dec 29

The investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA) was developed by the Auckland Cancer Society Research Centre (ACSRC). It has recently completed Phase I trials in New Zealand and UK under the direction of the Cancer Research Campaign's Phase I/II Clinical Trials Committee. As a biological response modifier, pharmacological and toxicological properties of DMXAA are remarkably different from most conventional chemotherapeutic agents. Induction of cytokines (particularly tumour necrosis factor (TNF-alpha), serotonin and nitric oxide (NO)), anti-vascular and anti-angiogenic effects are considered to be major mechanisms of action based on in vitro and animal studies. In cancer patients of Phase I study, DMXAA also exhibited various biological effects, including induction of TNF-alpha, serotonin and NO, which are consistent with those effects observed in in vitro and animal studies. Preclinical studies indicated that DMXAA had more potent anti-tumour activity compared to flavone-8-acetic acid (FAA). In contrast to FAA that did not show anti-tumour activity in cancer patients, DMXAA (22 mg/kg by intravenous infusion over 20 min) resulted in partial response in one patient with metastatic cervical squamous carcinoma in a Phase I study where 65 cancer patients were enrolled in New Zealand. The maximum tolerated dose (MTD) in mouse, rabbit, rat and human was 30, 99, 330, and 99 mg/kg respectively. The dose-limiting toxicity of DMXAA in cancer patients included acute reversible tremor, cognitive impairment, visual disturbance, dyspnoea and anxiety. The plasma protein binding and distribution into blood cells of DMXAA are dependent on species and drug concentration. DMXAA is extensively metabolised, mainly by glucuronidation of its acetic acid side chain and 6-methylhydroxylation, giving rise to DMXAA acyl glucuronide (DMXAA-G), and 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA), which are excreted into bile and urine. DMXAA-G has been shown to be chemically reactive, undergoing hydrolysis, intramolecular migration and covalent binding. Studies have indicated that DMXAA glucuronidation is catalysed by uridine diphosphate glucuronosyltransferases (UGT1A9 and UGT2B7), and 6-methylhydroxylation by cytochrome P450 (CYP1A2). Non-linear plasma pharmacokinetics of DMXAA has been observed in animals and patients, presumably due to saturation of the elimination process and plasma protein binding. Species differences in DMXAA plasma pharmacokinetics have been observed, with the rabbit having the greatest plasma clearance, followed by the human, rat and mouse. In vivo disposition studies in these species did not provide an explanation for the differences in MTD. Co-administration of DMXAA with other drugs has been shown to result in enhanced anti-tumour activity and alterations in pharmacokinetics, as reported for the combination of DMXAA with melphalan, thalidomide, cyproheptadine, and the bioreductive agent tirapazamine, in mouse models. Species-dependent DMXAA-thalidomide pharmacokinetic interactions have been observed. Co-administration of thalidomide significantly increased the plasma area of the plasma concentration-time curve (AUC) of DMXAA in mice, but had no effect on DMXAA's pharmacokinetics in the rat. It appears that the pharmacological and toxicological properties of DMXAA as a new biological response modifier are unlikely to be predicted based on preclinical studies. Similar to many biological response modifiers, DMXAA alone did not show striking anti-tumour activity in patients. However, preclinical studies of DMXAA-drug combinations indicate that DMXAA may have a potential role in cancer treatment when co-administered with other drugs. Further studies are required to explore the molecular targets of DMXAA and mechanisms for the interactions with other drugs co-administered during combination treatment, which may allow for the optimisation of DMXAA-based chemotherapy.
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PMID:5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. 1220 91


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