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

Nine of 48 adult patients who underwent orthotopic liver transplantation developed significant clinical neurological abnormalities recognized shortly after operation. Decrease in consciousness occurred with resultant coma, focal and generalized seizures and the occasional appearance of a state of akinetic mutism. Neuropathological abnormalities consisted of multifocal areas of infarction in cerebral cortex and basal ganglia in five patients, central pontine myelinolysis in five (often more extensive than usually reported), Wernicke's encephalopathy in three, glial nodules in two, and fungal abscesses in one. Alzheimer II astrocytosis was found in all brains available for retrospective study. There was direct evidence in two of the patients that air embolization from the homografts had occurred. Correlation of this with the brain infarcts in these and other cases seems reasonable. The ease with which air passed to the systemic circulation is explicable by the right to left venous--arterial shunts that are common in chronic liver disease. With the delination of this cause for the neurologic complications, measures to prevent it in future cases have been described.
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PMID:Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus. 34 84

Chronic liver disease typical of chronic active 'lupoid' hepatitis together with cyanosis, clubbing and hypertrophic osteoarthropathy in a 42-year-old female is described. In addition she had severe nose bleeds, gastro-intestinal haemorrhages, syncopal attacks with generalised convulsive seizures, pulmonary arterio-venous fistulae as manifestations of Rendu-Osler-Weber syndrome. A study of the literature revealed that similar associations are far more frequent than can be attribtued to chance. Possible mechanisms of the cyanosis, clubbing and osteoarthropathy and possible common pathogenesis for these seemingly unrelated disorders are discussed.
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PMID:Lupoid hepatitis, Rendu-Osler-Weber syndrome, clubbing cyanosis and hypertrophic osteoarthropathy. 105 21

Increased intracranial pressure is present in more than 80% of patients with fulminant hepatic failure. However, patients with encephalopathy secondary to chronic liver disease are thought not to develop elevated intracranial pressure. We report two patients with chronic liver disease in hepatic coma with raised intracranial pressure documented by an epidural intracranial pressure monitor. One patient rapidly deteriorated to coma over a period of 4 h. The other patient progressively worsened following intravenous sedation administered during upper endoscopy. Both patients had generalized tonic-clonic seizures, and one demonstrated decerebrate posturing and papilledema. Although all metabolic and structural abnormalities should be excluded in patients with hepatic encephalopathy, if the etiology remains in question, the possibility of increased intracranial pressure should be considered in patients with chronic liver disease.
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PMID:Increased intracranial pressure and hepatic encephalopathy in chronic liver disease. 161 43

We reviewed the clinical histories and autopsy records of 35 pediatric patients (ranging in age from 9 months to 18 years) who underwent orthotopic liver transplantation using ciclosporin and corticosteroids for immunosuppression. At the time of death, 19 children (54%) had encephalopathy, 16 (46%) were lethargic or in coma, 10 (29%) had seizures, and 10 were normal. Neuropathological lesions were found on postmortem examination in all 35 patients. Vascular lesions such as infarction, ischemia, thrombosis, and hemorrhage were the most common neuropathological findings (86%) followed by infectious processes (29%). Candida albicans (2 patients) and Aspergillus fumigatus (3 patients) were the only offending organisms identified, both causing meningoencephalitis. Alzheimer type II astrocytes, a characteristic feature of chronic liver disease, were the single most common autopsy finding (69%). Central pontine myelinolysis was seen in 3 children and basilar artery thrombosis affected 1 child. Neurological complications and their subsequent neuropathology are a significant cause of morbidity and mortality after pediatric liver transplantation. Vascular insults, electrolyte abnormalities, and infections that involve the central nervous system are directly related to liver function and the immunosuppression necessary to maintain graft viability. Only with continued observation after surgery combined with rapid medical and surgical treatment can we hope to improve the prognosis following liver transplantation in the pediatric population.
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PMID:Neuropathology of pediatric liver transplantation. 248 84

Phenytoin kinetics during long-term alcohol use and withdrawal were studied in 11 male alcoholics with a history of withdrawal seizures and no evidence of chronic liver disease. Ethanol, 20% v/v, was given for 6 days after admission to maintain the blood alcohol level between 500 and 800 mg/l and phenytoin suspension, 150 mg, was given orally or intravenously (on three occasions) every 12 hr for 20 days. The mean (+/- SD) total phenytoin clearance in 9 of 11 subjects was 0.023 +/- 0.006 l/kg/hr during the alcohol ingestion period. Clearance rose to 0.033 +/- 0.013 l/kg/hr (P less than 0.05) during alcohol withdrawal. Total steady-state concentration after 3 wk ranged from 3.4 to 29.9 mg/l, while the weight-corrected dose range was only 3.7 to 5.5 mg/kg/day. Inter- and intra-subject variation in bioavailability was small (0.93 to 1.03). Phenytoin free fractions ranged from 9.09% to 17.75% and changes in total and free phenytoin concentration correlated (r2 = 0.92, P less than 0.001). The data are compatible with the hypothesis that increased phenytoin clearance during alcohol withdrawal is due to the increased metabolic rate of the drug secondary to enzyme induction by ethanol, which becomes unmasked on cessation of drinking. In most alcoholics standard-dose phenytoin (300 mg/l) will induce lower than usual plasma concentrations.
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PMID:Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics. 727 3

Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.
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PMID:Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. 947 3

The liver is the major site of biotransformation for most opioids. Thus, the disposition of these drugs may be affected in patients with liver insufficiency. The major metabolic pathway for most opioids is oxidation. The exceptions are morphine and buprenorphine, which primarily undergo glucuronidation, and remifentanil, which is cleared by ester hydrolysis. Oxidation of opioids is reduced in patients with hepatic cirrhosis, resulting in decreased drug clearance [for pethidine (meperidine), dextropropoxyphene, pentazocine, tramadol and alfentanil] and/or increased oral bioavailability caused by a reduced first-pass metabolism (for pethidine, dextropropoxyphene, pentazocine and dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, and clearance of morphine was found to be decreased and oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administration. Lower doses or longer administration intervals should be used to remedy this risk. Special risks are known for pethidine, with the potential for the accumulation of norpethidine, a metabolite that can cause seizures, and for dextropropoxyphene, for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine, respectively. If metabolism is decreased in patients with chronic liver disease, the analgesic action of these drugs may be compromised. Finally, the disposition of a few opioids, such as fentanyl, sufentanil and remifentanil, appears to be unaffected in liver disease.
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PMID:Pharmacokinetics of opioids in liver disease. 1045 81

In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the dose. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and buprenorphine, which undergo primarily glucuronidation, and remifentanil which is cleared by esther hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys and may accumulate in patients with renal insufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With high concentrations they may cause narcotic effects or respiratory depression. In addition, special risks are known for normepridine that has been shown to exert neurotoxic effects with the risk of seizures. Few cases of respiratory depression following the administration of codeine, dihydrocodeine and tramdol have been reported. The elimination half-life of these drugs was prolonged. Lastly, the disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appears to be unaffected in renal failure. In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decreased drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil) and increased oral bioavailability due to reduced first-pass metabolism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and its oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administrations. As for patients with renal failure, special risks are known for meperidine with potential accumulation of normeperidine, which can cause seizures, and for propoxyphene for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine. In the case of reduced metabolism in chronic liver disease, the analgesic action of these drugs may be compromised. Lastly, the disposition of a few opioids, such as fentanyl, sufentanil, and remifentanil, appears to be unaffected in liver disease.
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PMID:[Therapy with opioids in liver or renal failure]. 1279 31

Neurologic complications (NCs) are a significant cause of morbidity and mortality in patients who undergo liver transplantation (LT). The aim of this study was to evaluate the incidence and type of NCs and associated factors in pediatric LT patients. We retrospectively reviewed NCs in the medical records of 40 consecutive infants, children, and adolescents who underwent LT at our institution. The subjects consisted of 23 boys and 17 girls (median age, 8.5 +/- 0.85 yr; range, 11 months to 17 yr). The indications for LT were Wilson's disease in 10 patients, fulminant hepatic failure (FHF) in nine, and other types of chronic liver disease in 21. NCs were found in 14 patients (35%). Those 14 individuals experienced a total of 16 episodes of NCs (two separate episodes in two of the patients). The most common NCs were seizure (seven episodes in six patients) and posterior leukoencephalopathy syndrome (PLES; five episodes in four patients). Seizure was the presenting symptom in three episodes of PLES. Two episodes of diffuse encephalopathy were observed in two patients, and two episodes of psychiatric symptoms occurred in two patients. We also noted one episode of tremor in one patient, one episode of acute dystonic reaction in one patient, and one episode of headache in one patient. Patients with Wilson's disease had a higher incidence of NCs (60%) than did patients without Wilson's disease (26.7%); however, this difference was not significant. The incidence of NCs was 44% in patients with FHF and 35% in those without FHF. That difference also was not significant. Immunosuppressive agents were the primary cause of 13 of the 16 episodes of NC. Uremia with hypertension, hypoxia, and hypomagnesemia caused one neurologic episode each. NCs, which are frequent in the first 30 days after pediatric LT, did not affect survival in this group. NCs were reversed by the discontinuation or reduction of immunosuppressive agents in 12 episodes, correction of hypomagnesemia and the reduction of immunosuppressive agents in one episode, and the correction of uremia and hypertension in one episode. Refractory epilepsy developed in one patient, and death unrelated to NCs occurred in one. The mortality rate was 7.1% (n = 1) in patients with NCs and 15.4% (n = 4) in those without NCs (p = 0.64). NCs are an important complication after LT. It is essential that each transplantation team collaborate with pediatric neurologists to ensure the rapid and accurate diagnosis of NCs in infants, children, and adolescents after LT and to prevent the delay of appropriate treatment.
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PMID:Neurological complications of liver transplantation in pediatric patients: a single center experience. 1730 Apr 94

Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. Here we report of two adult patients with a long history of epilepsy treated with PB who died suddenly: one as consequence of cardiac arrest, the other of acute bronchopneumonia. At autopsy, analysis of liver parenchyma revealed rich portal inflammatory infiltrate, which consisted of mixed eosinophil and monocyte cells, associated with several foci of necrosis surrounded by a hard ring of non-specific granulomatous tissue. Inflammatory reactions of internal and external hepatic biliary ducts were also seen. Our findings illustrate that PB may be associated with chronic liver damage, which may lead to more serious and deleterious consequences. For this reason, each clinician should recognize this entity in the differential diagnosis of PB-related asymptomatic chronic hepatic enzyme dysfunction.
Seizure 2007 Oct
PMID:Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients. 1757 47


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