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)

Fifty-two patients with advanced gastrointestinal (GI) malignancies who had not received previous chemotherapy or radiation therapy were randomized to be treated either with 24-hour infusion of weekly fluorouracil (5-FU) or the same plus N-(phosphonacetyl)-L-aspartic acid (PALA). Forty-seven patients were evaluable for the assessment of toxicity and antitumor activity. PALA was administered as an intravenous (IV) bolus over 15 minutes at a fixed dose, 250 mg/m2. The latter agent was administered 24 hours before the start of 5-FU infusion. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 3,400 mg/m2. In both arms of the randomized study, the courses were repeated every week. In both arms of the study, ataxia and myelosuppression were the dose-limiting toxic effects. At 5-FU dose of 3,400 mg/m2, one patient in each arm developed grade 3 hematologic toxicity. Other reversible side effects included grade 2 skin changes, nausea, and vomiting. During the administration of 2,600 mg/m2 of 5-FU over 24 hours, the steady state plasma 5-FU concentration was approximately 20 mumol/L. The maximum tolerated dose (MTD) for 5-FU for protracted treatment is 2,600 mg/m2 in either arm of the study. Therapeutic response was predominantly seen in the combination arm: there were two patients with complete response (CR) and 11 patients with partial response (PR) of 28 patients in the study. In the 5-FU alone arm there were four PR and 19 patients in the study.
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PMID:A randomized phase I and II study of short-term infusion of high-dose fluorouracil with or without N-(phosphonacetyl)-L-aspartic acid in patients with advanced pancreatic and colorectal cancers. 337 60

The currently recognized toxic effects of quinine in humans are identified and the problems of management of overdosage of quinine are discussed. Quinine, available therapeutically as sulphate or hydrochloride salts, also is widely used in tonic water, and there are several case reports of allergic reactions to the drug when a patient has consumed the drug in this way. Another unintentional source of poisoning is its use as an adulterant in heroin for "street" use. This appears to be a problem in the US. Quinine, termed a "general protoplasmic poison" is toxic to many bacteria, yeasts, and trypanosomes, as well as to malarial plasmodia. Quinine has local anesthetic action but also is an irritant. The irritant effects may be responsible in part for the nausea associated with its clinical use. In addition it has a mild antipyretic effect. Several features are common to both an acute single overdose in self-poisoning and accumulation of quinine during therapy for malaria: together they are termed cinchonism. Auditory symptoms, gastrointestinal disturbances, vasodilatation, sweating, and headache occur with moderately elevated plasma quinine concentration. As these rise, increasingly severe visual disturbances and then cardiac and neurologic features occur. Mild nausea may be the only symptom, but with large overdoses profuse vomiting, abdominal pain, and diarrhea may occur. These result from a combination of the local irritant effect of quinine on the gut and the central effects of quinine on the chemoreceptor trigger zone. Vasodilatation and sweating are well recognized, and tinnitus is common. Visual symptoms usually are delayed, and blindness may not be discovered for a day or more. Aspirin-sensitive patients, and others, may develop angioedema by nonimmunological mechanisms in response to drugs, and quinine has been reported to produce pseudo-allergic reactions in aspirin-sensitive patients. Quinine also can cause drug-induced thrombocytopenia and purpura. In patients suffering with malaria due to "Plasmodium falciparum," anemia and acute intravascular hemolysis with renal failure are recognized complications. There appears to be little evidence in the literature in support of the folk tradition of quinine as an inducer of abortion. Quinine is known to cause deterioration in patients with myasthenia gravis and erythema multiforme, to stimulate insulin release in patients receiving treatment for falicparum malaria, and to be responsible at times for ataxia following moderate overdosage. Clinically, quinine poisoning is observed in 3 situations: self-poisoning; accidentally; and following use of quinine in excessive doses in the hope of achieving abortion. Treatment courses are reviewed.
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PMID:Quinine toxicity. 354 70

Exposure to 1,3-dinitrobenzene (1,3-DNB) in humans induces methaemoglobinaemia, nausea and nervous symptoms. When given to conventional rats, twice-daily oral doses of 10 mg kg-1 1,3-DNB produce methaemoglobinaemia and frequently ataxia after four or five doses. In germ free rats given only a single oral dose of 20 mg kg-1, similar symptoms occur but are of more rapid onset. Light and electron microscope examinations reveal an acute thiamine deficiency-like lesion in the brain stems of both ataxic and apparently normal rats. Bilaterally symmetrical vacuolated lesions involve cerebellar roof, vestibular and superior olivary nuclei and the inferior colliculi. Frequent petechial haemorrhages are associated with these lesions, the erythrocytes usually being limited to enlarged Virchow-Robin spaces but sometimes spreading more widely. The primary cellular targets appear to be astrocytes, oligodendrocytes and vascular elements with secondary neuronal involvement. It is suggested that 1,3-DNB interferes with intracellular redox mechanisms resulting in impaired glucose oxidation.
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PMID:1,3-Dinitrobenzene-induced encephalopathy in rats. 368 48

Appropriate use of carbamazepine for the treatment of epilepsy is based on correct identification of the patient's seizure type. Carbamazepine is effective against partial seizures and against generalized tonic clonic seizures. Therapy should begin gradually, with initial doses increased slowly over 1 or 2 weeks, as tolerated. Side effects include fatigue, dizziness, ataxia, double vision, nausea, and vomiting. Most practitioners agree that, because of carbamazepine's relatively short half-life, the total dosage should be administered in at least two divided doses. This avoids too high a peak blood level that would occur with a single dose. Carbamazepine therapy is associated with the development of two hematologic conditions. Leukopenia, which may be transient or persistent, requires careful monitoring but is not cause for immediate discontinuation of therapy. Aplastic anemia occurs rarely but is potentially fatal, and therefore diligent monitoring of hematologic function is indicated. Aplastic anemia is an idiosyncratic, non-dose-related side effect that is most likely to occur within the first 3 or 4 months of initiating therapy. Once seizures are controlled, plasma levels of carbamazepine should be measured to establish optimum levels for individual patients being treated with this drug.
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PMID:How to initiate and maintain carbamazepine therapy in children and adults. 369 21

Spirogermanium, a heavy metal compound in which germanium has been substituted in an azaspirane ring structure, was studied in 39 patients with advanced malignant neoplasms. Thirty-one patients were considered evaluable for toxic effects of spirogermanium. Transient neurological symptoms occurred in 12 patients (39%), including dizziness or lightheadedness, marked fatigue, visual blurring, ataxia, paresthesia, and nausea. These symptoms could be reduced by infusing the drug over 2 hours rather than over 1 hour. Persistent neurotoxicity in the form of partial loss of taste or extreme weakness was observed in three patients. No evidence of hematologic, renal, or hepatic toxicity was observed. Antitumor activity of spirogermanium was not identified in this group of heavily pretreated patients. Spirogermanium had limited and acceptable toxicity in utilizing a dose of 120 mg/m2 infused over 2 hours, three times weekly.
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PMID:A phase II study of spirogermanium in advanced human malignancy. 390 6

A series of 12 patients with cerebellar infarcts diagnosed by computerized tomography are reviewed. The clinical features of cerebellar infarctions cover a wide spectrum, mimicking symptoms and signs from an acute labyrinthitis to a rapidly expanding posterior fossa mass lesion with brain stem and cerebral dysfunction. Two patients were asymptomatic and three showed signs of cerebellar dysfunction only. Three patients had evidence of brain stem dysfunction with cranial nerve palsies accompanying the cerebellar deficit. Two presented a pseudovestibular form with sudden onset of nausea, vomiting, rotary dizziness and ataxia. A pseudotumoral form with intracranial hypertension was found in two cases, in which softening tissue acts as a rapidly expanding posterior foss mass lesion. It is difficult to identify the exact artery involved in a cerebellar infarct because of the collateral circulation and connections between the three major arteries. Atherosclerosis and general decrease in blood flow can be regarded as the most likely factors precipitating focal cerebellar infarction. Surveillance is necessary during the first days with anti-edematous therapy. Rapid deterioration of consciousness should be considered a sign of increasing intracranial pressure progressing with the development of hydrocephalus. If necessary, surgical decompression by external drainage or by direct access to the posterior fossa can be carried out.
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PMID:[Cerebellar infarct. Clinical presentation and x-ray computed tomography of the brain]. 394 88

A group of 23 professional divers was investigated before and after dives to 300 and 350 metres of sea water. 12 divers were also studied during the actual dive. All divers presented neurological symptoms and signs during compression. Intention tremor, ataxia, motor weakness, sensory symptoms, vertigo, nausea and reduced memory were the most prominent features of the High Pressure Nervous Syndrome (HPNS). There were considerable individual differences. Neuropsychological and neurophysiological investigations performed after one dive showed no significant changes in any of the divers, while there was a clear-cut impairment in a group of 6 divers who had performed 2 dives 3 months apart. These changes indicate that there may be pressure-induced brain dysfunction which persists for a transient post-dive period. Loss of short-term memory is a prominent part of this dysfunction. Transitory neurological signs indicating focal cerebral dysfunction were found immediately post-dive in 4 divers, presumably reflecting the unmasking of pre-existing subclinical minimal CNS lesions.
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PMID:Central nervous dysfunction associated with deep-sea diving. 397 49

A 44-year-old man presented with symptoms of periodic ataxia, dysarthria, nausea and excessive sweating during the last twenty years. These symptoms could be provoked by physical or emotional stress and disappeared after bedrest for several hours. No other members of his family were known to have such complaints. Acetazolamide (Diamox) proved effective in preventing these symptoms. A disturbance of tryptophan metabolism is suggested as a cause of this disorder.
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PMID:Non-familial periodic ataxia responding to acetazolamide. 398 40

We conducted a pilot study of fluzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial.
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PMID:Pilot study of fluzinamide (N-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) in refractory partial seizures. 402 65

We describe two patients with paraneoplastic cerebellar syndromes who gained clinically useful neurologic remissions following radical excision of the primary cancer. In both patients the syndrome was characterized by the rapid onset of gait ataxia, nausea, postural vertigo, central positional nystagmus, and saccadic oscillations. These observations encourage radical treatment of the primary cancer in patients with advanced malignant neoplasms who are disabled by cerebellar dysfunction, and lend support to a current hypothesis that paraneoplastic cerebellar degeneration is due to anticerebellar Purkinje cell antibodies elaborated by the primary cancer.
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PMID:Paraneoplastic cerebellar disease. Remission with excision of the primary tumor. 406 21


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