Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three children were observed to have extensive liver injury following protracted seizures. Two recovered with supportive care and one died from central nervous system complications. When first measured, the levels of aminotransferases were minimally elevated, but they increased to 250 to 8,000 times normal within 12 to 24 h after the seizure episode. They fell to near normal over the next 8 to 11 days in the survivors, and to one sixth of the peak level by 4 days in the patients who died. A percutaneous liver biopsy from one child demonstrated centrolobular necrosis consistent with severe ischemic injury. Common causes for liver dysfunction, including viral hepatitis, drug hepatitis, and Reye syndrome, were excluded on clinical, serologic, and histologic grounds. We reason that hepatic injury resulted from ischemia. We speculate that prior treatment with anticonvulsants, which are capable of inducing mixed-function oxidases in the liver, aggravated the ischemia-reperfusion injury by increasing the production of reactive oxygen intermediates and reducing cytoprotective mechanisms. Prevention of such injury should be directed toward control of seizures and early respiratory support when seizures occur, not restructuring medication regimens.
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PMID:Acute liver injury after protracted seizures in children. 262 20

Monitoring modalities unique to the neurologic intensive care unit include intracranial pressure monitors and neuroelectrophysiologic monitors. Each modality fullfills criteria for accuracy, responsivity during clinical change, and stability over time for trend analysis. Intracranial pressure monitoring may be accomplished by any of three approaches--ventricular catheter, subarachnoid bolt, or epidural pressure transducer. Intracranial pressure control has proved beneficial in at least three different illnesses--acute closed head injury, acute noncommunicating hydrocephalus, and Reye's syndrome. Other illnesses, such as cerebral hemorrhage, near drowning, meningitis, encephalitis, and cerebral mass lesions, are often associated with ICP elevations. Neuroelectrophysiologic monitoring encompassing electroencephalography (EEG), signal-processed EEG, and evoked potentials has proved to be most beneficial to the intensive care setting. Evoked potentials are most useful for monitoring patients in drug-induced coma or muscle paralysis in whom a clinical neurologic examination is unreliable. Focal neurologic deficits, incipient brainstem ischemia, and possibly brain death can be deduced from multimodality-evoked potentials (brainstem auditory and somatosensory). Evoked potential apparatus can be used to record sequential stimuli and trend changes. Signal-processed EEG apparatus (compressed spectral array and cerebral function monitor) are used to assess global or regional EEG activity for longer periods of time. Interpretation of signal-processed EEG recording requires some experience with this technique, but it is much easier to interpret than a standard 16-lead EEG. These monitors are useful in evaluating some forms of abnormal EEG activity and in monitoring gross changes in global or regional electrical activity. Currently available technology offers dynamic insight into the management of acute neurologic illnesses. The technology in evoked potential and signal processed EEG monitoring will eventually reduce the size and complexity of the instrumentation, making its application routine. Intracranial pressure monitoring is already routine in many intensive care units, although its use is occasionally sporadic. We believe that application of appropriate neurologic monitors improves therapy and outcome in neurologically injured and ill patients.
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PMID:Neurologic intensive care unit monitoring. 391 79

We compared the levels of hormones and metabolites in the plasma of 37 survivors of Reye's syndrome with the levels in 8 fatal cases, at four time periods within 72 hours of admission. The most prominent differences were found for norepinephrine (NE), which was significantly elevated in fatal cases compared with survivors at all periods. Lactate and dopamine were elevated in the earlier periods. Epinephrine and alpha-amino acid nitrogen were also elevated in fatal cases, but the differences usually were not significant. NE elevation may reflect an increased sympathoadrenal medullary output associated with brain edema, compounded by impaired hepatic clearance of monoamines. Skeletal muscle ischemia from NE-induced vasoconstriction may explain the association between lactic acidemia and the severity of encephalopathy.
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PMID:The metabolic course of Reye's syndrome: distinction between survivors and nonsurvivors. 395 18

We report a fatal case of a child presenting Reye's syndrome associated with a variety of arrhythmias and ischemia-like ST-T ECG changes. At autopsy, fatty infiltration and patchy myocytolysis were detected in sections of the heart. This case report emphasizes cardiac involvement in Reye's syndrome and the possible mechanisms of arrhythmias in this disease.
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PMID:Arrhythmias and ischemia-like ECG changes in Reye's syndrome. 885 40

Opening of a non-specific, high conductance permeability transition pore or megachannel in the inner mitochondrial membrane causes onset of the mitochondrial permeability transition, which is characterized by mitochondrial swelling, depolarization and uncoupling. Inducers of the permeability transition include Ca2+, oxidant stress and a permissive pH greater than 7.0. Blockers include cyclosporin A, trifluoperazine and pH < 7. Using laser scanning confocal microscopy, we developed techniques to visualize onset of the mitochondrial permeability transition in situ in living cells. In untreated cells, the permeability transition pore is continuously closed and does not 'flicker' open. By contrast, the pore opens in liver and heart cells after exposure to oxidant chemicals, calcium ionophore, hypoxia and ischemia/reperfusion, causing mitochondrial uncoupling and aggravation of ATP depletion. In injury to hepatocytes from tert-butylhydroperoxide, an analog of lipid hydroperoxides generated during oxidative stress, onset of the mitochondrial permeability transition is preceded by oxidation of mitochondrial pyridine nucleotides, mitochondrial generation of oxygen radicals and an increase of mitochondrial Ca2+, all inducers of the mitochondrial permeability transition. In ischemia, the acidosis of anaerobic metabolism protects strongly against cell death. During reperfusion, recovery of pH to normal levels is a stress that actually precipitates cell killing. Onset of the mitochondrial permeability transition may be responsible, in part, for this pH-dependent injury, or pH paradox. The mitochondrial permeability transition may also be responsible for a variety of pathological phenomena. In particular, the mitochondrial permeability transition may underlie Reye's syndrome and Reye's-like drug toxicities. In conclusion, multiple mechanisms contribute to cell injury after hypoxia, ischemia/reperfusion and toxic chemicals, but a common final pathway leading to acute cellular necrosis may be ATP depletion after mitochondrial failure. One important mechanism causing mitochondrial failure is the mitochondrial permeability transition, which both uncouples oxidative phosphorylation and accelerates ATP hydrolysis. Interventions that block this pH-dependent phenomenon protect against onset of cell death.
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PMID:The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury. 930 81

Using confocal microscopy, onset of the mitochondrial permeability transition (MPT) in individual mitochondria within living cells can be visualized by the redistribution of the cytosolic fluorophore, calcein, into mitochondria. Simultaneously, mitochondria release membrane potential-indicating fluorophores like tetramethylrhodamine methylester. The MPT occurs in several forms of necrotic cell death, including oxidative stress, pH-dependent ischemia/reperfusion injury and Ca2+ ionophore toxicity. Cyclosporin A (CsA) and trifluoperazine block the MPT in these models and prevent cell killing, showing that the MPT is a causative factor in necrotic cell death. During oxidative injury induced by t-butylhydroperoxide, onset of the MPT is preceded by pyridine nucleotide oxidation, mitochondrial generation of reactive oxygen species, and an increase of mitochondrial free Ca2+, all changes that promote the MPT. During tissue ischemia, acidosis develops. Because of acidotic pH, anoxic cell death is substantially delayed. However, when pH is restored to normal after reperfusion (reoxygenation at pH 7.4), cell death occurs rapidly (pH paradox). This killing is caused by pH-dependent onset of the MPT, which is blocked by reperfusion at acidotic pH or with CsA. In isolated mitochondria, toxicants causing Reye's syndrome, such as salicylate and valproate, induce the MPT. Similarly, salicylate induces a CsA-sensitive MPT and killing of cultured hepatocytes. These in vitro findings suggest that the MPT is the pathophysiological mechanism underlying Reye's syndrome in vivo. Kroemer and coworkers proposed that the MPT is a critical event in the progression of apoptotic cell death. Using confocal microscopy, the MPT can be directly documented during tumor necrosis factor-alpha induced apoptosis in hepatocytes. CsA blocks this MPT and prevents apoptosis. The MPT does not occur uniformly during apoptosis. Initially, a small proportion of mitochondria undergo the MPT, which increases to nearly 100% over 1-3 h. A technique based on fluorescence resonance energy transfer can selectively reveal mitochondrial depolarization. After nutrient deprivation, a small fraction of mitochondria spontaneously depolarize and enter an acidic lysosomal compartment, suggesting that the MPT precedes the normal process of mitochondrial autophagy. A model is proposed in which onset of the MPT to increasing numbers of mitochondria within a cell leads progressively to autophagy, apoptosis and necrotic cell death.
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PMID:The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. 971 96