Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 10-year-old boy with the hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome is described. With dietary restriction of protein intake and supplementary administration of L-ornithine and L-arginine, the high concentration of ammonia decreased and the clinical signs of truncal ataxia and lethargy improved. A deficiency of ornithine transport into liver mitochondria was demonstrated biochemically, and glycogen granules and smooth surface endoplasmic reticulum were increased, but mitochondria showed normal construction ultrastructurally. Cranial computed tomography (CT) showed diffuse white matter low density and cerebellar vermis atrophy. The impairment of ornithine transport and energy production in the central nervous system may be related to the cranial CT findings and neurological signs.
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PMID:Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. 340 56

The effects of phenytoin (PHT) on the modifications of ammonia (NH+4) metabolism caused by sodium valproate (VPA) are here studied in order to identify the drug combinations susceptible of evoking stuporous states in epileptics, a rare condition attributed to a hyperammonemic encephalopathy induced by VPA. During chronic treatment with PHT or VPA-PHT, the acute injection of VPA increases the kidney's output of NH+4. During chronic PHT treatments, the acute injection of VPA modifies the liver's NH+4 metabolism and the arterial hyperammonemia is high (mean = 90 mumol/l). During chronic VPA-PHT treatments, the acute injection of VPA does not affect the hepatic NH+4 metabolism, suggesting that adaptation occurs, and the arterial hyperammonemia is moderate (mean = 60 numol/l). Disturbances of the hepatic adaptive mechanisms may explain certain complications observed during multiple-drug regimens.
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PMID:Adaptation of hepatic ammonia metabolism after chronic valproate administration in epileptics treated with phenytoin. 392 65

Three female infants with citrullinemia were followed clinically, biochemically and by electroencephalography. All three had episodes of vomiting, lethargy and hyperammonemia shortly after birth. The two more severe cases developed convulsions. They were saved by peritoneal dialysis, or repeated exchange transfusions followed by dietary adjustment. Multifocal spikes or repetitive paroxysmal activity of various kinds were seen in the EEGs at times of crisis. There was a lag in the EEG returning to normal after ammonia levels had returned to normal. Citrulline remained elevated in all cases. Follow-up over years revealed mild spasticity, mental retardation and, in one case, cortical atrophy.
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PMID:The EEGs of infants with citrullinemia. 399 77

Ozone, a lower-airway irritant, produces fatigue, lethargy, and increased respiratory rates in several species, including man. Ammonia, an upper-airway irritant, produces burning of the eyes, nose, and throat, and a decrease in respiratory rate. The effects of exposure to these two prototypical irritants were examined to see if behavioral changes during and after exposure occurred at concentrations comparable to those that produce symptoms in humans. Long-Evans rats and Swiss mice, individually housed in running wheels, were exposed either to ozone (0.08, 0.12, 0.25, or 0.5 ppm) or to ammonia (100 or 300 ppm) for 6 hr. Each animal's behavior was compared with its own control performance. Running in both species decreased in a concentration-related manner during exposure to either irritant. The decrease in running activity produced by high concentrations of ozone persisted for several hours after exposure. Concentrations of ammonia that eliminated running during exposure led to an increase in activity following exposure. At comparable concentrations of both compounds, activity in rats decreased more than in mice.
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PMID:Alterations in behavior produced by inhaled ozone or ammonia. 409 73

Mice intravenously injected with concentrated infectious influenza B/Lee/40 virus (LD50 = 6400 hemagglutinin units) developed lethargy, seizures, coma, and death 1 to 3 days later. The cerebrospinal fluid cell count was normal. Serum glutamic oxaloacetic transaminase levels increased 19-fold and plasma ammonia levels elevated 2.6-fold over control values. Serum bilirubin levels remained normal. Microvesicular fatty metamorphosis developed in the liver, whereas the brain showed mild cerebral edema without inflammatory changes. Viral propagation did not occur in liver or brain, but viral hemagglutinin, neuraminidase, and probably nucleoprotein antigens were produced in hepatocytes. Many of the clinical, biochemical, and pathologic features of the mouse illness are similar to those seen in Reye's syndrome.
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PMID:Experimental influenza B virus toxicity in mice. A possible model for Reye's syndrome. 629 39

Stuporous states induced by sodium valproate (VPA) are accompanied by an isolated marked hyperammonemia. In reality, hyperammonemia occurs after administration of VPA even in the absence of neurological complications. The hyperammonemia is of purely renal origin and results from modifications in glutamine metabolism, this compound being the main precursor of amino acid neurotransmitters. Combined administration of VPA and phenobarbitone increases the level of hyperammonemia due to lack of detoxification by the liver of the excess of ammonia produced by the kidneys. The anatomical site of origin of the ammoniogenesis, and its intensity, were studied in two patients with a history of stuporous states during combined VPA-phenobarbitone treatment. A single injection of VPA at a later date when they were being treated by combined phenobarbitone-carbamazepine therapy, induced disturbances in ammonia metabolism which did not differ qualitatively from those observed when intolerance to VPA is lacking. It is therefore not possible to rely on simple biological tests to detect patients at risk. Correlation is also lacking between the degree of hyperammonemia and disorders of vigilance. Ammonia does not therefore appear to be the only factor responsible for neurological complications and the role of other factors must be investigated. These include: disturbances of metabolism of inhibitory and excitatory aminoacid neurotransmitters, the condition of the cerebral parenchyma, and the excitatory effect of sodium valproate which could act to varying degrees in synergy with the hyperammonemia to provoke a stuporous state.
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PMID:[Role of hyperammonemia in stuporous states induced by sodium valproate]. 642 Aug 66

A young adult patient suddenly began to have episodes of unconsciousness that each lasted for several hours. Brief episodes of lethargy occurred monthly. Biochemical tests disclosed high levels of ammonia and citrulline in the serum. Brain oedema was suggested by CT scan, and optic disc swelling was observed ophthalmoscopically, indicating papilloedema. He died in coma. Deficient activity of argininosuccinate synthetase in the liver was demonstrated. Papilloedema was confirmed histologically. We believe that papilloedema is a serious sign indicating poor prognosis in late-onset citrullinaemia.
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PMID:Papilloedema in late-onset citrullinaemia: report of second case. 647 7

In five spontaneous outbreaks, sixty-four BALB/cByJ mice developed Reye's-like syndrome 4 to 33 days after introduction into mouse rooms known to harbor a variety of indigenous murine viruses. The clinical course lasted 24 hours and consisted of progressively deteriorating consciousness and hyperventilation, usually leading to death. Mice killed and necropsied while stuporous or comatose had serum ammonia levels of 2524 +/- 179 versus 66 +/- 8 micrograms/dl for control BALB/cByJ mice. Necropsy findings included swollen, diffusely pale yellow livers with panlobular microvesicular fatty change, pale renal cortices with epithelial fat droplets of the proximal convoluted tubules, and Alzheimer type II astrocytosis of the neocortex, corpus striatum, hippocampus, and thalamus. In three of the five outbreaks involving 66% of affected animals, mice had active coronaviral enteritis. Electron microscopic changes in hepatocytes, neocortical astrocytes, and neurons were similar to or identical with those described for the acute phase of Reye's syndrome in man. The epizootiology of these outbreaks and the apparent synchrony between Reye's syndrome-like illness and the stage of intestinal coronavirus infections in some of these outbreaks suggest that one or more naturally occurring murine viruses were of etiologic significance.
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PMID:Spontaneous Reye's-like syndrome in BALB/cByJ mice. 648 84

A symptomatic elevation in plasma ammonium concentration, termed hyperammonemia, is associated with numerous congenital and acquired conditions (Table 11). In some cases, such as urea cycle disorders, ammonia is the principal toxin. In other instances, such as portal systemic encephalopathy, it is but one of a number of metabolic disturbances, However, in either case hyperammonemic episodes should be treated aggressively to prevent coma, subsequent brain damage, or death. This involves restricting protein intake, providing adequate calories, and giving agents that remove accumulated nitrogen. Long-term therapy relies on diagnosing the specific disease rate. This rarely requires invasive procedures such as liver biopsy. In most cases measurement of plasma amino acids and urinary organic acids will identify the defect. Treatment involving restriction of nitrogen intake, vitamin supplementation, or stimulation of alternative pathways of waste nitrogen excretion can then be instituted. Early therapy, especially in patients with neonatal-onset hyperammonemia, is imperative to avoid severe brain damage. On this basis, the plasma ammonium level should be determined in virtually every newborn with lethargy, hypotonia, poor feeding, seizures, and/or respiratory distress of unclear origin (Table 12).
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PMID:Hyperammonemia. 651 17

Visual evoked potentials were utilized to examine the neuronal transmission changes provoked by galactosamine-induced hepatic encephalopathy and by administration in normal animals of toxins presumably involved in the pathogenesis of hepatic encepalopathy. Separate acute administrations of ammonia, dimethyldisulfide, and octanoic acid induced lethargy, convulsions in the case of the first two, and coma with visual-evoked potential patterns that never resembled the evoked potentials recorded in hepatic coma. By contrast, single and repeated administrations of the three above-mentioned toxins together at lower doses induced lethargy and coma with visual-evoked potential patterns similar to those observed in galactosamine-induced hepatic coma. These observations, together with previously published data, are consistent with the concept that the synergistic interaction of these toxins plays a significant role in the pathogenesis of hepatic encephalopathy.
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PMID:Visual evoked potentials in encephalopathy induced by galactosamine, ammonia, dimethyldisulfide, and octanoic acid. 711 66


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