Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep patterns were recorded during 5 weeks of chronic treatment with sodium barbital and after abrupt cessation of drug administration. Sodium barbital was administered intragastrically to adult cats twice daily in doses to produce a peak response of gross ataxia ("low-dose" barbiturate treatment). Sleep stages were scored from EEG, EOG, and neck EMG recordings from chronically implanted electrodes. Sleep was monitored continuously for 48 h once each week during barbital administration and continuously for 7 to 10 days during withdrawal. Rapid eye movement (REM) sleep during barbital treatment was reduced to approximately half compared with control. At the end of the treatment, equivalent doses of pentobarbital were substituted for barbital. Cessation of pentobarbital administration produced withdrawal. Withdrawal intensity was moderate and spontaneous convulsions occurred in half the animals. The duration of withdrawal insomnia was 2 to 3 days. Return of the non-REM and REM sleep was associated with changes in withdrawal behaviors, notably the appearance of overly affectionate behavior. Furthermore, during return of sleep both non-REM and REM sleep increased to values greater than control.
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PMID:Sleep patterns in cats during chronic low-dose barbiturate treatment and withdrawal. 653 86

The silver salt of 2-metanilamido-5-chloropyrimidine (AgMCP) and the sodium, amminosilver and trimethylphosphite-silver salts of 3',5'-dichlorobenzenesulfonanilide (NaDBS, AgNH3DBS and AgP(OCH3)3DBS were synthesized as possible antibiotic of antiparasitic drugs. All the organosilver compounds were extremely water-insoluble. For animal studies these, and other reference compounds, were given as fine suspensions in an Emulphor-safflower oil mixture. The ip LD50's in mice in mmol/kg were: 1.67 for NaDBS, 0.22 for silver acetate (AgAc), 0.15 for AgP(OCH3)3DBS, 0.13 for AgMCP and 0.10 for AgNH3DBS. When given by mouth, 15 mmol AgAc/kg produced a high mortality, but none of the organosilver compounds caused death in maximal doses (1.9 to 2.6 mmol/kg) that could be given based on considerations of total volume and stability of the suspension. All the silver compounds, including AgAc, produced a similar toxic syndrome with initial hyperexcitability, ataxia, central nervous depression, labored breathing, loss of righting reflex and death. Most deaths occurred between 12 and 24 hours after dosing. In contrast, animals given NaDBS often died within 3 hours although the major signs were very similar to those produced by the silver compounds. When given ip as a single dose 30 minutes after AgAc, D-penicillamine was effective in reducing mortality, but it had no effect on the mortality of the organosilver compounds. Histological studies revealed similar patterns of silver deposition, especially in the liver and kidneys, at 6, 18 and 24 hours after the organosilver compounds and after AgAc. We conclude that the presence of silver contributes significantly to the acute toxicity of these sulfonamides although they may dissociate free silver less readily than does AgAc.
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PMID:Acute toxicity of some silver salts of sulfonamides in mice and the efficacy of penicillamine in silver. 662 59

A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm. Sodium phenobarbital was administered orally twice daily for 35 days in individually adjusted doses to achieve mean daily peak CNS depression culminating in severe ataxia. Dose to dose continuity of CNS depression was maintained throughout treatment. At the time of dosing rats were mildly ataxic. Following abrupt termination of chronic treatment, an abstinence syndrome characterized by CNS hyperexcitability was observed, which demonstrates physical dependence. Signs, which included motor, autonomic, and behavioral manifestations, appeared from 12-24 h and animals recovered by 12 days. Although tolerance development was nearly complete on day 10 of treatment, the abstinence syndrome observed was more severe following 35 than after 10 days of chronic treatment. Characteristics of tolerance and physical dependence are similar to those described for other species including humans.
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PMID:Phenobarbital tolerance and physical dependence: chronically equivalent dosing model. 668 22

Of 1,994 yearling and 2-year-old cattle in a winter feeding program, 117 died within 42 days of being fed toxic amounts of monensin sodium in a liquid protein supplement. Death losses commenced on the third day after ingestion of a toxic amount in the feed. Clinical signs in cattle that died in less than 9 days included anorexia, pica, diarrhea, depression, mild hindlimb ataxia, and dyspnea. Gross necropsy findings in cattle dying in the acute phase of the illness included hydrothorax, ascites, and pulmonary edema, as well as petechial hemorrhages, edema, and yellow streaking in skeletal and cardiac muscle. Cattle dying after 9 days had gray streaks in heart and skeletal muscle, generalized ventral edema, enlarged, firm, bluish discolored liver, and enlarged heart. Microscopic changes in cattle dying in the acute phase (less than 9 days) consisted of pulmonary edema, congestion, and hemorrhage. Cardiac and skeletal muscle had localized areas of edema, hemorrhage, and coagulative necrosis. In cattle dying after 9 days of illness, the changes included lymphocytic infiltration, sarcolemmal nuclear proliferation, and fibrosis in skeletal and cardiac muscle. Lungs contained increased alveolar macrophages and a few neutrophils. Centrilobular necrosis and mild fibrosis were found in the liver. Changes varied somewhat according to the area of heart or skeletal muscle that was affected. Active muscles, eg, those in the heart ventricles and diaphragm, were altered most severely. Intoxication appeared to be a result of sedimentation of monensin in the molasses carrier to give remarkable concentrations of the substance at the bottom of the holding tank.
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PMID:Accidental monensin sodium intoxication of feedlot cattle. 673 46

The relationship between the plasma concentration of valproic acid (VPA) and anticonvulsant or neurotoxic effects was studied in the rat. Anticonvulsant activity was assessed against; (1) maximal seizures induced either by electroshock or by intravenous injection of pentylenetetrazol; and (2) kindled amygdaloid epilepsy. Drug-induced neurotoxicity was determined by the rotarod test and by observation of behaviour. In the maximal seizure tests, tonic hindlimb extension was always abolished at plasma valproic acid concentrations of 225 microgram ml-1 and above. Tonic forelimb extension was not consistently blocked until the plasma drug concentration exceeded 530 microgram ml-1. In fully-kindled rats, plasma valproic acid concentrations of 300 microgram ml-1 and above markedly reduced the duration of amygdala afterdischarge activity and the intensity of behavioural seizures produced by amygdala stimulation. Analysis of the data from individual kindled rats revealed that there was a significant correlation between the estimated plasma concentration of valproic acid and the degree of seizure protection. Impairment of rotarod performance and marked ataxia occurred at plasma valproic acid concentrations above 510 microgram ml-1 and loss of righting reflex became evident at 970 microgram ml-1. From these results, it is concluded that the plasma concentration of valproic acid is closely correlated with the anticonvulsant and neurotoxic effects observed in individual rats after acute administration of sodium valproate.
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PMID:The relationship between plasma concentration of valproic acid and its anticonvulsant and behavioural effects in the rat. 681 Jan 97

Aqueous and organic extractions of ground seeds of Cassia occidentalis were obtained. Chickens were dosed with extracted material to assess the toxicity of the extracts. Organic extracts with methanol, ethanol, chloroform, ethyl acetate, and benzene were ineffective in removing the toxin from the seeds. Aqueous extractions, using 25 mM sodium bicarbonate or 250 mM sodium citrate, removed the toxin from the seeds, but left the toxin bound to particulate matter in the extract. Addition of Triton X-100 to the aqueous buffers effectively solubilized the toxin from the particulate matter. Signs of intoxication in the chickens were loss of weight, weakness, diarrhea, hypothermia, occasionally ataxia, and recumbency; then death. Gross lesions included paleness of skeletal and cardiac muscles and congestion of the liver. Microscopic lesions in muscle tissue were vacuolation, proliferation of sarcolemmal nuclei, and separation of myofibrils. Electron microscopic examination revealed disruption of mitochondrial cristae and swelling and rupture of mitochondria.
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PMID:Preliminary isolation of a myodegenerative toxic principle from Cassia occidentalis. 688 74

Human and animal eosinophils contain a powerful neurotoxin that causes selective neuronal and axonal damage to white matter of cerebellum and spinal cord of experimental animals when injected intrathecally. This reaction is termed the "Gordon phenomenon." We purified the eosinophil-derived neurotoxin from eosinophil-rich leukocyte suspensions or eosinophil granules from four patients with various hypereosinophilic syndromes. A single protein with an average molecular weight of 18,400 was isolated by sequential chromatography on Sephadex G-50 columns and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis of column fractions. The purified eosinophil-derived neurotoxin from the cells of these patients retained the potent neurotoxic activity of the crude eosinophil or eosinophil granule extracts in experimental animals. These animals developed the syndrome of stiffness and ataxia progressing to severe paralysis characteristic of the Gordon phenomenon. Histologic examination of the brains of animals injected with purified eosinophil-derived neurotoxin confirmed the characteristic widespread loss of Purkinje cells and severe spongiform vacuolation in the white matter of cerebellum, brain stem, and spinal cord. We have established the location of eosinophil-derived neurotoxin in the eosinophil granule and have shown that it is distinct from several other eosinophil proteins, the granule major basic protein, and the Charcot-Leyden crystal protein (lysophospholipase).
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PMID:Purification of human eosinophil-derived neurotoxin. 694 62

Severe neurological symptoms, including intermittent ataxia, hallucinations and convulsions, associated with metabolic acidosis and branched-chain amino-acidemia occurred in a six-year-old girl with a variant form of maple syrup urine disease. The symptoms only appeared during periods of infection. Between these periods the girl was healthy and the biochemical findings were normal. In later episodes of infection the condition was successfully treated with a low protein diet and sodium bicarbonate. Analyses of 1-14C-leucine decarboxylase in fibroblasts revealed 10 per cent of normal activity in the girl and 50-70 per cent in the parents. The importance of early diagnosis of MSUD variants is discussed. This is the first published Swedish case of MSUD variant.
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PMID:Intermittent neurological symptoms in a girl with a maple syrup urine disease (MSUD) variant. 720 7

The initial treatment of trigeminal neuralgia is accomplished with drugs, primarily carbamazepine and occasionally phenytoin sodium. However, many patients become refractory to treatment or side effects develop such as drowsiness or ataxia. In these circumstances, surgical therapy is appropriate. At our institution, microsurgical decompression has yielded good to excellent results in 29 of 32 patients and is currently recommended for persons in good general health who are younger than 70 years. Because of the notable incidence of unpleasant dysesthesias in the face, percutaneous radiofrequency rhizotomy is reserved for persons whose age or general medical condition precludes craniotomy.
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PMID:Management of trigeminal neuralgia (tic douloureux). 723 Apr 94

1 Patients with poorly controlled epilepsy were cautiously transferred from multiple drug therapy to treatment with phenytoin sodium alone. One patient suffered more severe seizures and the initial treatment was restarted. The remainder showed no deterioration. 2 The daily dose of phenytoin was then increased by a small increment at intervals of 2 or more months. The serum phenytoin concentration (total and free) was measured regularly and response was assessed by records of seizure frequency and tests of speech, handwriting, short-term memory and coordination. 3 Patients (n = 11) with partial seizures showed no consistent improvement with increased phenytoin concentration within the range 15 mg/l (60 mumol/l) to the individual threshold for intoxication, greater than or equal to 35 mg/l (140 mumol/l). Patients (n = 4) with generalized seizures however were consistently improved at higher concentrations. 4 Tolerance to phenytoin varied, the threshold for symptomatic intoxication ranging from 35-60 mg/l (140-240 mumol/l) total and 2.7-5.2 mg/l (10.8-20.8 mumol/l) free. Ataxia was the commonest symptom and in some cases this was manifest by worsening of performance on the test of coordination (pursuit rotor). Even at lower phenytoin concentrations the patients performed less well on this test than control subjects. Other tests of performance showed no evidence of impairment at higher phenytoin concentrations. 5 The same daily dose of phenytoin tended to give higher serum drug concentrations after intoxication than before.
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PMID:Serum phenytoin concentration and clinical response in patients with epilepsy. 734 Aug 85


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