Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

gamma-Aminobutyric acid (GABA) agonists have been proposed for the treatment of tardive dyskinesia, but their therapeutic potential has been limited by side effects and toxicity. To elucidate further the role of GABA in neuroleptic-induced dyskinesias, we evaluated tetrahydroisoxazolopyridinol (THIP), a new, less toxic GABA analog and GABA receptor agonist, in both a dose-finding (single-dose) pilot study with five patients and a longer (four-week) placebo-controlled study with 13 patients. The patients were videotaped during a standardized examination; tardive dyskinesia, parkinsonian symptoms, and eye-blinking rates were rated blindly and randomly. The maximal short-term dose of THIP was 10 to 25 mg, whereas in the longer-term study the highest daily dose ranged from 20 to 120 mg. Tardive dyskinesia was unchanged during THIP treatment, but preexisting parkinsonism increased significantly and eye-blinking rates decreased. Psychiatric symptoms showed no significant changes, although tension and depression lessened. Side effects included sedation, confusion, dizziness, vomiting, and myoclonic jerks. Although THIP is not an effective new treatment for tardive dyskinesia, more specific GABA agonists should be evaluated in future studies of this syndrome.
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PMID:The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia: a new gamma-aminobutyric acid agonist. 612 70

Twelve parallel, open, uncontrolled therapeutic studies on 3-fluoro-6-(4-methyl-piperazinyl)- 11H -dibenz[b,e]azepine ( fluperlapine , NB-106 689) were performed as a multicenter trial using standardized protocol/case report forms and inclusion and global assessment criteria. 66% of 104 medium to severe acute or relapsed schizophrenic patients showed a very good or good overall benefit (responder rate 80%) with 200-400 mg fluperlapine daily, median 300; 20-1200 mg; 6 weeks. Ratings ( FSCL -NL = (Fischer Symptom Check List Neuroleptics, BPRS = Brief Psychiatric Rating Scale, FSUCL = Fischer Somatic Symptoms and Untoward Effects Check List) showed a quick onset of action (25% improvement in 5 days) and a very good improvement of all important and secondary single symptoms or symptom groups. FSCL -NL and BPRS were highly correlated (R = 0.87). Tolerability was very good or good in 88% of patients (very good in 65%, poor or bad in 12%), mild to moderate fatigue being the most prominent untoward effect (means 25% of patients, max. 31 per control) followed by dizziness, tremor, dry mouth (10%). No drug-induced Parkinsonism was seen. No recurrent or relevant abnormalities in relation to fluperlapine were observed in safety data (circulation, blood, kidney or liver function). Several times paroxysmal dysrhythmias/sharp waves were seen in the EEG, and in our studies 2 patients experienced epileptiform seizures of short duration after overdosage. In one patient showing a granulocytopenia before starting fluperlapine , an agranulocytosis was seen, which normalized quickly after stopping fluperlapine .
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PMID:Fluperlapine in 104 schizophrenic patients. Open multicenter trial. 614 28

Fluperlapine, a new clozapine-like neuroleptic drug with weak affinity for dopamine receptors, was evaluated in a blind, placebo controlled trial in 11 patients with stable hyperkinesia (ten with tardive dyskinesia (TD) and one with spontaneous dyskinesia). Drug effects during active treatment (200-600 mg/day) and during pre- and post-treatment placebo periods were determined by scoring randomly sequenced videotapes of TD and parkinsonian symptoms recorded weekly during standardized examinations. TD score was unchanged, while parkinsonism slightly decreased (P less than 0.05) and eye-blinking rates increased (P less than 0.05). Psychiatric symptoms showed no significant changes, although positive psychotic symptoms diminished in four patients. Side effects included dizziness, sedation and constipation. The effects in movement disorders found in this study may imply that fluperlapine is less liable than traditional neuroleptics to induce acute extrapyramidal side effects and tardive dyskinesia and is particularly beneficial in the treatment of patients vulnerable to neurological side-effects.
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PMID:Fluperlapine in tardive dyskinesia and parkinsonism. 614 95

From our investigations, we are tempted to assume that all types of akinesia, including "freezing", off-phases, Yo-Yoing and akinetic crises, are primarily symptoms of PD, while hyperkinesia, stretch spasms and pharmacotoxic psychosis are "side-effects". Therefore side-effects can be triggered by antiparkinsonian therapy while they will disappear after withdrawal of the drugs inducing them. Antiparkinson drugs alleviate major symptoms like akinesia and rigidity but sometimes and especially as reflection of advanced parkinsonism, might amplify minor symptoms (freezing, off-phases, Yo-Yoing), which then predominantly at high drug doses occur earlier and more intensively. Therefore, minor symptoms can be observed more frequently in the advanced stages of PD. Depressed phases belong to the symptom complex as is bradyphrenia and dizziness. Bradyphrenia is the psychic correlate to akinesia. Dementia, if at all is a symptom, but more likely this disease occurs occasionally in combination with parkinsonism.
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PMID:Symptoms and side effects in the course of Parkinson's disease. 658 6

A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking. Physical examination revealed a masked oily face with slight cerebellar disturbance. Abnormality of autonomic function tests was recognized and he was diagnosed as Shy-Drager syndrome with gradually progressing, diffuse autonomic failure accompanied by slight cerebellar ataxia and Parkinsonism. Both serum sodium level and plasma osmotic pressure were reduced, whereas daily sodium excretion was more than 100mEq and urinary osmolality was about 500mOsm/kgH2O. His renal function was intact, and the adrenocortical and thyroid hormone levels were normal, then criteria of SIADH was fulfilled. SIADH was thought to have occurred on the basis of Shy-Drager syndrome. Water load test showed failure of adequate water diuresis, but intravenous phenytoin administration following the water load test ameliorated the diuresis to normal. The relationship between plasma osmolality and the ADH response indicates that ADH was adequately secreted in response to the increase in plasma osmolality but not suppressed in response to the decrease in plasma osmolality below 280mOsm/kgH2O. These results suggest that ADH synthesis in the hypothalamus and its secretion from the pituitary gland were both intact. The response of ADH secretion to the orthostatic hypotension induced by head-up tilt was quite blunted, being compatible with Shy-Drager Syndrome. Sleep disturbance was studied by polysomnography and laryngoscopy, and was revealed to be based upon severe sleep apnea due to incomplete paralysis of the bilateral vocal cords. Sleep apnea due to vocal cord paralysis is sometimes found to be complicated in patients with multiple system atrophy (MSA) including Shy-Drager syndrome, and is known as Gerhardt syndrome. This is the first report on a case of Shy-Drager syndrome complicated with SIADH and bilateral vocal cord paralysis. In this case, SIADH is caused by impaired afferent pathways from baroreceptors to the hypothalamus, which transfer inhibitory stimuli on ADH secretion. It is suggested that Shy-Drager syndrome should be considered one of the causes of SIADH.
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PMID:[A case of Shy-Drager syndrome complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and incomplete paralysis of bilateral vocal cords]. 795 87

This chapter reports the clinical and neuropathological findings of eight cases of "diffuse Lewy body disease" verified by autopsy. The age at onset was between 60 and 82 years; the age at death was between 75 and 92 years. The initial symptoms were amnesia in three cases, orthostatic dizziness in three, visual hallucination in two, but parkinsonism in none. The cardinal clinical symptoms included dementia in all cases, hallucinatory-delusional state in six, akinesia and rigidity in five, and orthostatic hypotension in five. Antemortem diagnoses were senile dementia in five, and hallucinatory-delusional state, Parkinson's disease and Shy-Drager syndrome in one each. Despite the clinical symptoms differences from each other, neuropathological findings were alike. Abundant Lewy bodies were present in the neurons of the cerebral cortex as well as in the brainstem nuclei and diencephalon. Concomitant senile changes including senile plaques and Alzheimer's neurofibrillary tangles (NFTs) were also present in varying degree. Immunocytochemical study with anti-ubiquitin for Lewy body, anti-tau protein for NFT, and beta-protein of amyloid for senile plaque suggested that dementia of DLBD might have resulted not from a single pathology but from the complex of Lewy bodies, NFTs and senile plaques.
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PMID:Clinical and neuropathological aspects of diffuse Lewy body disease in the elderly. 842 Jan 71

The patient with Parkinson's disease often needs concomitant treatment for disorders that accompany the disease, such as depression, insomnia or constipation, or for frequent concomitant alterations such as dizziness, high blood pressure or heart disease. The many drugs that can worsen motor symptoms in Parkinson's disease must be avoided, especially if use will be prolonged. Not all drugs that induce or aggravate parkinsonism have the same potency. We describe 3 groups: 1) drugs that invariably induce or aggravate parkinsonism if taken long enough or at high enough doses; 2) drugs that only provoke parkinsonism in some individuals, and 3) drugs that interfere with the action of levodopa. Knowledge of these drugs is essential for all doctors who treat patients with Parkinson's disease.
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PMID:[Drug treatment of frequent disorders in patients with Parkinson's disease]. 869 42

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of L-dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on-off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 +/- 14.9 vs 9.0 +/- 16.1; p = 0.0184). By the end of maintenance, the mean reduction in L-dopa requirement was -150.7 mg for pramipexole-treated patients compared to -10.6 for placebo-treated patients. The most common adverse events (< 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.Copyright Lippincott-Raven Publishers
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PMID:A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease. 1021 Aug 37

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun
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PMID:[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning]. 1050 96

Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Both are used, often simultaneously, as adjuncts to L-dopa/dopa decarboxylase (DDC) inhibitor treatment of Parkinson's disease (PD). Their possible interactions have not been previously studied in a double-blind manner.We studied clinical response, tolerability, haemodynamics and cardiac rhythm in 16 PD patients with end-of-dose-type motor fluctuations. The patients' individual L-dopa/DDC inhibitor treatment was stabilized before the experimental treatments. This was followed by three consecutive, randomized, double-blind 2-week treatment periods with entacapone (200mg with each L-dopa dose), selegiline (10mg o.d.) or both entacapone and selegiline with the L-dopa/DDC inhibitor medication. Clinical efficacy (L-dopa test with repeated motor and dyskinesia scoring) and safety (orthostatic test, 24-h ambulatory ECG, haematological and clinical chemistry variables and adverse events) evaluations were performed before each treatment (control) and at the end of each treatment period.All three treatments, entacapone, selegiline, and entacapone+selegiline as adjunct to L-dopa/DDC inhibitor improved (p<0.05) clinical disability compared to L-dopa only but they did not differ significantly from each other. Dyskinesias increased with all the treatments, statistically significantly (p<0.01) with entacapone+selegiline. No significant differences in haemodynamics were observed between control and any of the experimental treatments, or between the experimental treatments in the orthostatic test. One patient already had symptomatic orthostatism before experimental treatments (control). In two other patients orthostatism emerged after the introduction of selegiline, and in one after every experimental treatment. Twenty-four-hour ECG did not show any differences in supraventricular or ventricular extrasystoles or heart rate between treatments. No statistically significant differences were observed in adverse events or in haematology and clinical chemistry variables. One patient treated with entacapone+selegiline discontinued the study due to dizziness and insomnia. Our results suggest that co-administration of entacapone with L-dopa/DDC inhibitor, with or without selegiline, improves clinical disability, is safe, but may also enhance dopamine-related adverse events to some extent in PD patients with end-of-dose type motor fluctuations.
Parkinsonism Relat Disord 2000 Oct 01
PMID:Entacapone and selegiline with L-dopa in patients with Parkinson's disease: an interaction study. 1090 Mar 96


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