Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...
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PMID:Intravenous administration of diazepam in patients with chronic liver disease. 101 18

Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation.
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PMID:Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction. 226 Mar 36

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
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PMID:[Hepatolenticular degeneration]. 226 49

Two cases of phenytoin toxicity in patients with chronic liver disease who were taking 300 mg phenytoin daily are described. Each patient developed encephalopathy, characterized by confusion, disturbed conscious state, asterixis, and nystagmus, which was resistant to treatment with protein restriction, lactulose, and neomycin, but responsive to withdrawal of phenytoin. We suggest that the phenytoin did not precipitate hepatic encephalopathy, but caused an encephalopathy that mimicked it. We recommend that phenytoin be used cautiously in patients with liver disease, and that the drug's unbound serum level be measured if encephalopathy occurs.
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PMID:Phenytoin toxicity and hepatic encephalopathy: simulation or stimulation? 361 89

Thirty-two cases of Wernicke's encephalopathy were admitted to hospital for treatment in a period of 33 months; this represented a relatively low incidence in total hospital admissions. Thiamin status was deficient, borderline and normal in 21 (66%), five (16%) and six (19%) patients, respectively, and responded immediately to treatment in those who had abnormal thiamin status. Ophthalmoplegia responded rapidly to treatment. Nystagmus, ataxia, disturbance of mental function and peripheral neuropathy responded incompletely to treatment in both the short-and the long-term. The overall setting for the development of Wernicke's encephalopathy appears to be chronic alcohol abuse, accompanied by cerebral "atrophy" and liver disease, but often without gross evidence of malnutrition.
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PMID:Wernicke's encephalopathy in a metropolitan hospital. A prospective study of incidence, characteristics and outcome. 394 14

The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.
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PMID:Neonatal cholestasis and hypopituitarism. 647 83

A 66-year-old man was admitted to Tokyo Metropolitan Geriatric Hospital because of progressive speech disturbance and ataxic gait. He had no history of abdominal surgery, liver disease, heavy drinking nor blood transfusion. One day before the admission, he showed confusional behavior for 6 hours, but he had no other history of consciousness disturbance. Neurological examination revealed slurred speech, fixation nystagmus, limb and gait ataxia, and hyperreflexia with pathological reflexes. Extrapyramidal signs were not identified. Laboratory examination showed marked hyperammonemia (118-292 micrograms/dl) with poor ICG excretion (ICG15 min = 30.8%). Percutaneous portography showed a large shunt vessel between the portal vein and the left hepatic vein. The plasma ammonium level of the right hepatic vein is normal (15 micrograms/dl), but that of the left one is very high (298 micrograms/dl). Therefore we concluded that hyperammonemia of the systemic circulation was resulted from portal-systemic shunt. A T2 weighted MRI image demonstrated symmetrical high signal intensity in the deep cerebral white matter. Unique lesions were observed in the bilateral middle cerebellar peduncles, and shown as low signal intensity in T1 weighted image and as high signal intensity in T2 weighted image. Hyperammonemia and neurological impairments of this patient did not improve with medical treatment. Three months after occlusion of the shunt vessel, fixation nystagmus and extensor plantar responses abolished and unsteadiness gait improved. Hyperammonemia might cause the cerebellar ataxia in the present case.
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PMID:[A case of portal-systemic shunt with progressive ataxia]. 833 93

Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology.
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PMID:Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase. 1820 4

Niemann-Pick type C (NP-C) disease is a neurovisceral lysosomal storage disease characterized by neurologic dysfunction, hepatosplenomegaly, and early death. Natural history studies are very difficult to perform due to the low incidence and high heterogeneity of disease in the human population. Sixteen cats with a spontaneously occurring missense mutation in NPC1 were evaluated over time to define the progression of neurologic and hepatic disease. Affected cats had remarkably regular onsets of specific signs of cerebellar and vestibular system dysfunction with progressive severity of dysfunction quantified by postrotatory nystagmus and brain stem auditory evoked response measures. NP-C disease cats also showed increasing serum activity of alanine aminotransferase, asparate aminotransferase, and cholesterol with advancing age. Affected cats lived to a mean age of 20.5 +/- 4.8 wk. CNS and hepatic lesions were similar to those described in human patients. These data are the first to document progressive hepatic disease in the feline model and demonstrate the importance of liver disease as part of the NP-C disease phenotype. Both neurologic and hepatic measures of disease onset and severity can be used as a baseline with which to assess the efficacy of experimental therapies of NP-C disease in the feline model.
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PMID:Clinical, electrophysiological, and serum biochemical measures of progressive neurological and hepatic dysfunction in feline Niemann-Pick type C disease. 1861 65

Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported autosomal recessive multiorgan disease. Herein, we propose that mutations in YARS underlie another clinical phenotype adding a second variant of the disease, including retinitis pigmentosa and deafness, to the spectrum of YARS-associated disorders.
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PMID:An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS. 2923 4


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