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)

The introduction of levodopa in the treatment of Parkinson's disease had modified both the prognosis and the current concepts of the disease, Although levodopa remains the most potent drug for the treatment of Parkinson's disease, its long-term use is associated with fluctuations in motor performance, abnormal movements and psychotic hallucinations. These late side-effects remain difficult to treat and thus raise questions as to the benefits and risks of first-time treatment with levodopa. Levodopa mainly alleviates akinesia and rigidity and to a lesser extent, tremor. Levodopa increases life expectancy. This paper reviews some recent developments in the pharmacology of Parkinson's disease. Recent findings indicate that not only central dopamine but also several other central neurotransmitter and receptor changes are involved in the pathophysiology of Parkinson's disease. New data on autonomic dysfunction in Parkinson's disease are presented. New methods of investigation (clinical rating scales, pharmacological tests, imaging techniques, etc.) are reviewed. Finally, future strategies, e.g. the development of potent new symptomatic drugs (selective D2 and D1 agonists, new formulations of apomorphine, COMT inhibitors, new routes of administration, etc.) and etiopathogenic agents (antioxidative and anti-free radical drugs, etc.) are discussed.
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PMID:Recent advances in the clinical pharmacology of Parkinson's disease. 168 24

L-DOPA and dopamine (DA) binding antibodies were found in the blood serum of Parkinsonian patients and middle-aged and elderly normal persons. DA-binding serum gamma-globulins of parkinsonian patients injected into rat caudate nuclei induced the pathogenetic mechanism of Parkinson's syndrome (generator of pathologically enhanced excitation) in these brain part and evoked main parkinsonian symptoms (oligokinesia, rigidity, tremor). The serum gamma-globulins of Parkinsonian patients without Da-antibodies caused less pronounced EEG disturbances. Parkinsonian symptoms developed rarely and were shorter and less pronounced compared with the DA-antibody effect. The DA binding antibodies role in Parkinson's syndrome pathogenesis and is L-DOPA therapeutic tolerance formation was discussed.
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PMID:[Dopamine antibodies in the pathogenesis of parkinsonism]. 172 56

Parkinson's disease (PD) is often associated with dementia in elderly patients, and sometimes PD coexists with senile dementia of the Alzheimer type (SDAT) or cerebrovascular disease (CVD) in the elderly. However, since there are few previous clinical studies on the coincidence of, or relationship between PD and CVD, the authors evaluated these aspects in 34 elderly patients with PD using MRI and SPECT. All the patients were over 70 years old. The diagnosis of PD was based on the presence of three symptoms (resting tremor, cogwheel rigidity and bradikinesia) which are characteristic of PD, and the effectiveness of L-DOPA therapy. We therefore believe that patients with vascular Parkinsonism were excluded from our study. In 34 cases, 24 (71%) had MRI evidence of CVD (mainly the lacunar state). In the 10 cases who had no CVD, 2 (20%) had severe dementia and the decrease of regional cerebral blood flow (rCBF) in the temporal and parietal lobes bilaterally correlated with the SPECT findings commonly found in SDAT. A comparison of the rCBF and the results of Hasegawa's dementia score (HDS) (verbal intelligence score) was made between the patients with PD associated with CVD and the patients with PD who had no CVD and no SPECT findings which correlated with SDAT. The rCBF in the frontal lobes and the results of the HDS of the former group were significantly lower than those of the latter. As mentioned above, elderly patients with PD often had CVD, leading to dementia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A clinical study in elderly patients with Parkinson's disease using MRI and SPECT--Parkinson's disease and the lacunar state]. 179 37

Bilateral administration of 6-hydroxydopamine in the medial fore-brain bundle at the level of the posterolateral hypothalamus in rats resulted in hypokinesia, muscular rigidity and tremor as determined by various behavioral assessment procedures. These neurological signs were accompanied by marked decreases in the concentrations of dopamine and its main metabolites dihydroxyphenylacetic acid and homovanillic acid in both striatum and nucleus accumbens. Administration of apomorphine (1 mg/kg) or L-Dopa (60 mg/kg) reversed or totally abolished the hypokinesia, rigidity and tremor in lesioned animals. Together, the present findings demonstrate that bilateral intrahypothalamic administration of 6-OHDA results in the appearance of the three cardinal symptoms of Parkinson's disease in rats. This model should prove to be valuable for both the study of the neuropathological processes underlying the neurological signs of this disease and the screening of potential antiparkinson agents.
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PMID:Hypokinesia, rigidity, and tremor induced by hypothalamic 6-OHDA lesions in the rat. 190 8

The present study compares 30 patients who developed idiopathic Parkinson's disease (PD) at the age of 48 years or younger and 47 patients who developed the disease at the age of 68 years or older. PD patients with early onset had rigidity and bradykinesia as the predominant features at onset and during the course of the illness. In contrast older onset patients exhibited more often tremor at the beginning while later in the course most of them developed the full triad of symptoms i.e. tremor-rigidity-bradykinesia. In spite of such differences the overall disability status did not differ between the two groups of patients. An additional observation was that the early onset patients were apter to show earlier and more often abnormal movements and response fluctuations related to the L-Dopa therapy.
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PMID:Clinical observations in early and late onset Parkinson's disease. 191 56

Several studies support the hypothesis of 5-HT (serotonin) involvement in the physiopathology of the extrapyramidal system. Ritanserin is a new compound with a high, selective, and long-lasting binding affinity for 5-HT2 receptors. A therapeutic effect of ritanserin has been reported in Parkinson's tremor and L-Dopa-induced dyskinesias but no effect was seen in essential tremor. In this double-blind comparative study with orphenadrine (150 mg daily p.o.) and placebo, ritanserin (30 mg daily p.o.) was administered to 36 schizophrenic outpatients who were being treated with neuroleptic drugs and who had parkinsonism. For a period of 3 weeks, the treatment was added to the antipsychotic therapy after a 7-day washout from previous antiparkinson medication. Psychopathology was rated weekly by the Brief Psychiatric Rating Scale and showed no significant changes during the trial. The Mindham Rating Scale was used to assess symptoms of parkinsonism; at week 3, ritanserin was superior to orphenadrine (p less than 0.03) and to placebo (p less than 0.01). The results confirm previous observations of the therapeutic efficacy of ritanserin on neuroleptic-induced parkinsonism, and support the hypothesis that serotonin influences extrapyramidal physiopathology.
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PMID:5-HT2 antagonist ritanserin in neuroleptic-induced parkinsonism: a double-blind comparison with orphenadrine and placebo. 212 57

The pathogenesis of essential tremor (ET) is evidently very complicated and involves various biochemical and pathophysiological mechanisms. The pathology of cerebral adrenergic systems is attributed a high value in the development of the disease. The general catecholamine (CA) metabolic indices were investigated in 40 ET patients. CA excretion was considerably decreased, especially that of norepinephrine, while the urinary level of a CA precursor DOPA was essentially normal. The excretion of a major epinephrine and norepinephrine metabolite vanillylmandelic acid also tended to decrease. Contrarily to the CA excretion, their blood levels did not change considerably. The data are supposed to point to a reduction of the general CA body pool, especially of norepinephrine. This yields the shift of relationship between lepinephrine and norepinephrine toward the latter, that can provide another mechanism for ET. Possible deterioration of noradrenergic neurotransmission as a pathogenic factor of ET, and adrenergic receptors hypersensitivity in particular, are still pending. Major genetically predetermined biochemical defect in ET leading to impaired control of complicated mechanisms behind the regulation of synchroneous activity of spinal motor structures, is believed to be closely related to CA systems modifying ET in response to various impacts and involving the mechanisms of central action alcohol.
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PMID:[Catecholamine metabolism in essential tremor]. 216 46

A single blind placebo-controlled study has been performed in order to investigate objectively the acute tremorolytic effect of oral L-Dopa in ten parkinsonians chronically treated with L-Dopa. Finger tremor was assessed by means of a computerized accelerometer method, at rest and during maintenance of a fixed posture. Both resting and postural tremor were significantly influenced by L-Dopa. An "acute test" with oral L-Dopa, especially when different tremor components are investigated, may be useful for identifying objectively parkinsonians whose tremor does not respond to drug therapy or shows a deterioration of drug-responsiveness.
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PMID:Tremor in Parkinson disease: acute response to oral levodopa. 220 64

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.
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PMID:Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. 230 73

Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.
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PMID:[An unusual association of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus associated with spontaneous pituitary apoplexy]. 230 57


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