Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic hyperammonemia (IHA) has been described as a rare complication of intensive chemotherapy, but there is little data regarding its occurrence after bone marrow transplantation (BMT). IHA is defined as elevated plasma ammonia concentrations (> 200 mumol/l) in the absence of significant liver function abnormality. From a 21 year BMT database of 2358 patients, we have identified 12 patients (0.5%) with IHA, ages 19 to 46 years. Diagnoses included ALL (n = 2), AML (n = 4), CLL (n = 1), CML (n = 3) and aplastic anemia (n = 2). Eight received marrow from a matched sibling donor, three from an unrelated donor and one autologous marrow. IHA occurred between 14 and 106 days after transplant (median, 25 days). Most frequently patients presented with symptoms of a metabolic encephalopathy, with lethargy and confusion evolving into unresponsiveness, metabolic coma and in eight cases, seizures. At diagnosis of IHA, liver functions were normal or only modestly abnormal. Ten of the 12 patients died 1 to 9 days (median 3.5 days) after diagnosis of IHA despite treatment with combinations of dialysis and ammonia-trapping therapy. While IHA is a rare complication of BMT, it is associated with a high mortality. Early recognition of the syndrome by measurement of plasma ammonia concentrations in patients with neurological symptoms may improve outcome.
 ...
PMID:Idiopathic hyperammonemia: a frequently lethal complication of bone marrow transplantation. 880 24

A 4-year-10-month-old boy with late infantile type neuronal ceroid lipofuscinosis was reported. He presented with progressive dementia, loss of visual acuity, gradual regression of speech and motor functions, and myoclonic jerks. A hyperactive deep tendon reflex was noted, but there was neither muscle weakness nor hepatomegaly. Serum lactate, pyruvate and ammonia levels were within normal limits. The funduscopic examination showed diffuse mottling of the retinal pigmented epithelium. The electroencephalogram showed irregular bilateral spike-and-waves or polyspike-and-waves and isolated focal spikes from the bilateral parieto-occipital regions. The wave forms of visual evoked potentials were flat. The electroretinogram was unrecordable. The somatosensory evoked potentials showed prolonged central conduction times from bilateral median nerves. The brainstem auditory evoked potentials were within normal limits. Diffuse cerebral and cerebellar atrophy were noted on magnetic resonance imaging. The diagnosis was confirmed by the electron-dense cytoplasmic inclusion bodies within the conjunctival squamous epithelial cells. No specific treatment was available. Regular anticonvulsants were not given during follow-up because seizures attacked him only on occasion. His visual acuity was progressively impaired. In addition to nearly total absence of speech, an inability to communicate and walk independently was also noted. The clinical features according to the subtypes, radiology, pathology, managements and prenatal diagnosis for this case are discussed.
 ...
PMID:Late infantile type neuronal ceroid lipofuscinosis: report of one case. 894 35

The purpose of this study was to determine the time of onset, duration, and the efficacy of in vivo gene transfer in protecting the ornithine transcarbamylase deficient spf/Y mouse from an acute ammonium challenge. The animals were challenged with ammonia (10 mmol/kg NH4Cl) 1, 2, 7, 14, or 28 d after the administration of a recombinant adenoviral construct deleted in E1 and with a temperature sensitive mutation in E2. Although there was no protection with the control LacZ virus, the ornithine transcarbamylase (OTC)-containing vector provided partial protection from both behavioral symptoms (ataxia, seizures, and abnormal response to sound) and biochemical abnormalities (ammonium, aspartate, alanine, and glutamine) within 24 h and complete protection by 48 h. Mortality was also decreased. Animals receiving the vector 7 and 14 d before the ammonium load were also protected, whereas those treated 28 d before the challenge were not. OTC enzyme activity in liver of untreated spf/Y mice was 5% of control C3H mice. After gene transfer, activity was increased to near control levels through 14 d but had returned to baseline by 28 d. These studies indicate that adenovirus-mediated gene transfer confers a metabolic benefit within 24 h of administration and provides protection against an acute metabolic insult for at least 2 wk.
 ...
PMID:Adenovirus-mediated in vivo gene transfer rapidly protects ornithine transcarbamylase-deficient mice from an ammonium challenge. 909 55

A 3-year-old male German shepherd dog was presented with severe generalised seizures. The dog was protein-intolerant and showed severe hyperammonaemia on ammonia stimulation. The hyperammonaemic state was present for at least 6 weeks and then spontaneously resolved. No obvious cause (liver disease, portocaval shunts, urea cycle enzyme deficiencies, drug therapy or urinary tract obstruction) could be identified. It is possible that this dog had a variation of transient hyperammonaemic syndrome, described in man and recently in a juvenile Irish wolfhound, that extended into adulthood.
 ...
PMID:Transient hyperammonaemia in an adult German shepherd dog. 929 Oct 77

Epileptic patients given phenobarbital (3 mg/kg, n = 8) or finlepsin (20 mg/kg, n = 7) were found to have a statistically significant increase (p < 0.05) in the parameters of the lipid peroxidation end product malonic dialdehyde in the erythrocytes (3.34 +/- 1.13 mumol/liter) and blood plasma (0.099 +/- 0.04 mumol/liter) in comparison to the control group (n = 9; 1.58 +/- 0.96 mumol/liter and 0.045 +/- 0.02 mumol/liter, respectively). The urea level (6.7 +/- 1.28 mumol/liter) and the ammonia level (31.59 +/- 10.46 mumol/liter) increase were statistically insignificant as compared to the controls (5.76 +/- 0.66 mumol/liter and 26.41 +/- 5.96 mumol/liter, respectively). Bemitil (n = -7) in a dose of 20 mg/kg reduced in 10 days the amount of malonic dialdehyde in the erythrocytes (1.57 +/- 0.61 mumol/liter, p < 0.05) and plasma (0.043 +/- 0.02 mumol/liter, p < 0.05) as well as the amount of urea (3.76 +/- 0.96 mumol/liter,) and ammonia p < 0.05 and ammonia (18.17 +/- 2.02 mumol/liter, p < 0.05) in the blood. A favorable therapeutic effect (lesser frequency of seizures and lesser asthenia of the of the children) was observed at the same time. The frequency of paroxysms reduced to 50% in 4 patients (2 with complex-partial seizures, one with absence, and one with simple-partial seizures) and to 75-% in the fifth patient with complex-partial seizures. The therapeutic effect in the 6th and 7th patients could not be evaluated.
 ...
PMID:[The effect of bemitil on the parameters of lipid peroxidation and nitrogen metabolism in epilepsy in children]. 932 90

Many neurologic disorders are related to congenital or acquired hyperammonemia (HA). Advanced symptoms of HA range from seizures in acute stages to stupor and coma in more chronic conditions, manifesting variable imbalance between the inhibitory and excitatory neurotransmission. Evidence obtained with the use of experimental HA models suggests that acute neurotoxic effects of ammonia are mediated by overactivation of ionotropic glutamate (GLU) receptors, mainly the N-methyl-D-aspartate (NMDA) receptors, and to a lesser degree the KA/AMPA receptors. NMDA receptor-mediated neurotoxicity may be potentiated by impaired control of their function by metabotropic GLU receptors, which are inactivated by ammonia. Prolonged overactivation of the NMDA receptors upon extended ammonia exposure causes their downregulation. The GLU receptor changes may be related to their excessive exposure to extrasynaptic GLU. Ammonia promotes GLU accumulation in the extrasynaptic space by enhancing its release from neurons, and/or by decreasing its reuptake to the nerve endings and astrocytes, where the effect results from inactivation (downregulation) of the astrocytic glutamate transporter GLT1. Excitotoxic effects of ammonia are augmented by increased synthesis of nitric oxide (NO), which is associated with NMDA receptor activation and/or increased synaptic transport of arginine (ARG). A shift toward neural inhibition is promoted by positive modulation of the gamma-aminobutyric acid (GABA)ergic tone resulting from excessive accumulation in the brain of endogenous central benzodiazepine receptor agonists, and from upregulation of astrocytic peripheral benzodiazepine receptors leading to elevated levels of prognenelone-derived neurosteroids, which positively modulate the GABA(A) receptor complex. Inhibitory neurotransmission may also be favored by enhanced release from astrocytes of an inhibitory amino acid, taurine.
 ...
PMID:Roles of neuroactive amino acids in ammonia neurotoxicity. 946 66

Congenital ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea cycle enzymes in humans. A large percentage of survivors of neonatal OTC deficiency suffer severe developmental disorders, including seizures, mental retardation and cerebral palsy. Neuropathological studies reveal ventricular enlargement, cerebral atrophy and delayed myelination, as well as Alzheimer type II astrocytosis. Using the sparse-fur (spf) mouse model of congenital OTC deficiency, studies of central cholinergic integrity revealed a developmental delay in choline acetyltransferase activity and of high-affinity [3H]-choline uptake in several brain structures. Subsequent studies of muscarinic cholinergic binding site distribution showed a widespread loss of M1 sites, consistent with cholinergic cell loss. These alterations are similar to those reported in Alzheimer's disease, suggesting that the severe cognitive dysfunction in congenital OTC deficiency may at least partly result from a muscarinic cholinergic lesion. Possible mechanisms involved in the pathogenesis of cholinergic cell loss in congenital OTC deficiency include ammonia-induced inhibition of pyruvate and alpha-oxoglutarate oxidation, resulting in decreased synthesis of acetyl CoA and a cerebral energy deficit, as well as NMDA receptor-mediated excitotoxicity. Treatment of spf mice with acetyl-L-carnitine (ALCAR) results in partial recovery of the developmental choline acetyltransferase deficit, suggesting a potential therapeutic benefit of ALCAR in congenital OTC deficiency. Other therapies currently used include ammonia-lowering strategies (using sodium benzoate or sodium phenylacetate) and, in severe cases, liver transplantation.
 ...
PMID:Evidence for a central cholinergic deficit in congenital ornithine transcarbamylase deficiency. 977 87

Although valproic acid has gradually gained its popularity in the treatment of various seizure disorders, overdose of valproate is not common. An 18-y-old man with a history of epilepsy controlled by sodium valproate and clonazepam attempted suicide with an ingestion of 45 g sodium valproate. He presented to our service with drowsiness and irritability. Extremely high serum ammonia (623 ug/dL) and elevated serum valproate concentration (575 ug/mL) were found on admission. Several metabolic abnormalities, including hypernatremia, hypocalcemia and metabolic acidosis, as well as, increased serum transaminase levels were also recorded. With supportive measures, he became clear 24 h later and was discharged 6 d after ingestion. Serial follow-up of his serum valproate and ammonia levels disclosed a close relationship between these 2 measurables. After acute overdose of valproic acid, patients usually present with mild and generally reversible depression of the central nervous system. However, impairment of liver function, hyperammonemia, fluid-electrolyte disturbances, coma, seizures, hypotension and even death may occur following valproate overdose. Symptomatic and supportive measures are the mainstay in the treatment of valproic acid overdose. With prompt diagnosis and early institution of treatment, a complete recovery should be anticipated.
 ...
PMID:A case of severe hyperammonemia and unconsciousness following sodium valproate intoxication. 983 Jun 96

The Pi peak in a 31P NMR spectrum of the brain can be deconvoluted into six separate Lorentzian peaks with the same linewidth as that of the phosphocreatine peak in the spectrum. In an earlier communication we showed that the six Pi peaks in normal brain represent two extracellular and four intracellular compartments. In that report we have identified the first of the extracellular peaks by marking plasma with infused Pi, thereby substantially increasing the amplitude of the single peak at pH 7.35. 2-Deoxyglucose-6-phosphate (2-DG-6-P) was placed in the brain interstitial space by microdialysis. The resulting 2-DG-6-P peak was deconvoluted into three separate peaks. The chemical shift of the principle 2-DG-6-P peak gave a calculated pH of 7.24 +/- 0.02 for interstitial fluid pH, a value that agreed well with the pH of the second extracellular Pi peak at pH 7.25 +/- 0.01. We identified the intracellular compartments by selectively stressing cellular energy metabolism in three of the four intracellular spaces. A seizure-producing chemical, flurothyl, was used to activate the neuron, thereby causing a demand for energy that could not be completely met by oxidative phosphorylation alone. The resulting loss of high-energy phosphate reserves caused a significant increase in intracellular Pi only in those cells associated with the Pi peak at pH 6.95 +/- 0.01. This suggests that this compartment represents the neuron. Ammonia is detoxified in the astrocyte (glutamine synthetase) by incorporating it into glutamine, a process that requires large amounts of glucose and ATP. The intraarterial infusion of ammonium acetate into the brain stressed astrocyte energy metabolism resulting in an increase in the Pi of the cells at pH of 7.05 +/- 0.01 and 7.15 +/- 0.02. This finding, coupled with our observation that these same cells take up infused Pi probably via the astrocyte end-foot processes, lead us to conclude that these two compartments represent two different types of astrocytes, probably protoplasmic and fibrous, respectively. As a result of this study, we now believe the brain contains four extracellular and four intracellular compartments.
 ...
PMID:NMR-based identification of intra- and extracellular compartments of the brain Pi peak. 983 54

Six enzyme defects of the urea cycle have been described. Ornithine transcarbamylase deficiency is the most frequent of these diseases. The cumulative frequency is 1:8000. Most patients become symptomatic in childhood, but onset of symptoms may occur later in childhood or even adulthood. The patients present with recurrent episodes of an unspecific acute encephalopathy, seizures and clouding of consciousness to a variable degree. Focal neurological signs such as hemiparesis, aphasia or ataxia may also occur. These episodes may be triggered by infection, protein overload or drugs. Diagnostic are increased blood ammonia levels. Characteristic patterns of plasma amino acids and the determination of orotic acid in the urine mostly discriminate the individual disorders. Further diagnostic steps include the allopurinol challenge test, liver or skin biopsy for measurement of enzyme activity and molecular genetic studies. Treatment requires restriction of protein intake, supplementation of arginine and activation of alternative pathways of nitrogen excretion with benzoate or phenylbutyrate. Untreated, the acute episode may be lethal. Long-term treatment improves the clinical outcome considerably. Urea cycle defects should be included in the differential diagnosis of any encephalopathy or coma of unclear origin, and blood ammonia should be determined early in the evaluation of such patients.
 ...
PMID:[Enzyme defects of the urea cycle in differential acute encephalopathy diagnosis in adulthood. Diagnosis and current therapy concepts]. 1009 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>