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)

Posterior leukoencephalopathy syndrome is a newly recognised brain disorder that predominantly affects the cerebral white matter. Oedematous lesions particularly involve the posterior parietal and occipital lobes, and may spread to basal ganglia, brain stem, and cerebellum. This rapidly evolving neurological condition is clinically characterised by headache, nausea and vomiting, seizures, visual disturbances, altered sensorium, and occasionally focal neurological deficit. Posterior leukoencephalopathy syndrome is often associated with an abrupt increase in blood pressure and is usually seen in patients with eclampsia, renal disease, and hypertensive encephalopathy. It is also seen in the patients treated with cytotoxic and immunosuppressive drugs such as cyclosporin, tacrolimus, and interferon alfa. The lesions of posterior leukoencephalopathy are best visualised with magnetic resonance (MR) imaging. T2 weighted MR images, at the height of symptoms, characteristically show diffuse hyperintensity selectively involving the parieto-occipital white matter. Occasionally the lesions also involve the grey matter. Computed tomography can also be used satisfactorily to detect hypodense lesions of posterior leukoencephalopathy. Early recognition of this condition is of paramount importance because prompt control of blood pressure or withdrawal of immunosuppressive agents will cause reversal of the syndrome. Delay in the diagnosis and treatment can result in permanent damage to affected brain tissues.
 ...
PMID:Posterior leukoencephalopathy syndrome. 1150 3

Preeclampsia is a hypertensive disorder unique to pregnancy and is of unknown cause. It is both a maternal as well as fetal syndrome. It affects 2%-10% of nulliparas, and is more prevalent when preexisting hypertension, renal disease, or diabetes is present. The main clinical features of the disorder are maternal hypertension, proteinuria, and abnormal renal, hepatic, and central nervous system function. The fetal syndrome includes growth restriction, intrauterine death, and premature delivery. Abnormalities in the development of the placental circulation are believed to be important causal features of the pathogensis of preeclampsia and are present early in pregnancy. The link between the placental disease and the maternal syndrome remains mysterious. Clinical trials of low dose aspirin and calcium in the prevention of preeclampsia have not demonstrated significant benefits of treatment. The current approach to treatment is close monitoring of maternal and fetal health, bed rest, judicious use of antihypertensive therapy to prevent maternal complications, and seizure prophylaxis with magnesium sulfate. (c)2000 by Le Jacq Communications, Inc.
 ...
PMID:Preeclampsia: New Thoughts on an Ancient Problem. 1141 34

This report describes nonconvulsive status epilepticus (NCSE) in four patients with end-stage renal disease (ESRD) on peritoneal dialysis therapy. All patients presented with acute confusion or stuporous state without clinical motor seizures. Three patients had active systemic infections and were being administered antibiotics. Diagnoses were confirmed in all cases by electroencephalogram (EEG), which showed characteristic diffuse sharp waves and spikes. The EEG appearance improved after anticonvulsant therapy. All patients had satisfactory control of their electrical seizure activity and made varying degrees of mental recovery. To our knowledge, this is the first reported series of NCSE in patients with ESRD on peritoneal dialysis therapy. It shows NCSE as a differential diagnosis for acute confusion. We emphasize the need for nephrologists to consider NCSE as a differential diagnosis for uremic encephalopathy.
 ...
PMID:Nonconvulsive status epilepticus in peritoneal dialysis patients. 1184 Mar 92

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.
 ...
PMID:Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view. 1155 Dec 37

Muromonab-CD3 is widely used for immunosuppression in patients undergoing solid organ transplant. We report two siblings with oligomeganephronia and end-stage renal disease who developed encephalopathy and seizures from muromonab-CD3 following renal transplant. The first case is a 13-year-old girl who developed encephalopathy, seizure, and triparesis following renal transplant while muromonab-CD3 was used for immunosuppression. The second case was the 6-year-old sister of the first case, who also developed recurrent focal seizures while she was on muromonab-CD3 for renal transplant immunosuppression. In both cases, a sequential brain magnetic resonance image (MRI) showed progression of abnormalities from the cerebral cortex to the white matter. In the first case, the MRI normalized after muromonab-CD3 was discontinued. In the second case, the patient developed a leukoencephalopathy following cyclosporin administration. The pathophysiology of muromonab-CD3 encephalopathy is believed to be a disturbance to the blood-brain barrier mediated by cytokine release from lymphocyte stimulation by muromonab-CD3. Because the major histocompatibility complex genes are known to regulate cytokine responses, it is possible that the excessive production of cytokines that causes encephalopathy may occur in patients who share close major histocompatibility complex genes. Muromonab-CD3 in a patient whose sibling has developed cerebral complications from its use should be administered with caution. The second case suggests that muromonab-CD3 encephalopathy predisposes patients to develop cyclosporin neurotoxicity. Because the pathogenesis of muromonab-CD3 encephalopathy and cyclosporin-related cerebral complications are both potentially mediated through a disturbance of the blood-brain barrier, it is possible that one agent may predispose a patient to the complication of the other.
 ...
PMID:Muromonab-CD3-induced neurotoxicity: report of two siblings, one of whom had subsequent cyclosporin-induced neurotoxicity. 1173 68

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.
 ...
PMID:Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients. 1190 37

We present 2 patients with HIV/AIDS and suspected HIV-associated nephropathy who presented with end-stage renal disease and new-onset seizures. These cases highlight the relationship between metabolic disorders and new-onset seizures in HIV-infected persons. Causes of new-onset seizures in this setting include opportunistic infections, HIV-associated dementia (AIDS dementia complex), and various metabolic disorders. A sizable proportion of patients had no identifiable cause of seizures despite extensive workup. In these instances, seizures can be attributed to subclinical effects--direct and indirect--of HIV on the brain. Seizures tended to be recurrent, sometimes despite anticonvulsant therapy. In a subset of patients, seizures were the initial presenting sign of HIV infection.
 ...
PMID:New-onset seizures as an initial presentation of end-stage renal failure in patients with HIV/AIDS. 1213 82

An 18-year-old male patient with MELAS phenotype and 2 previous episodes of cerebral stroke, recurrent seizures and nephropathy, was treated with creatine monohydrate after the acute onset of psychomental regression and changing states of somnolence and aggressive and agitated behaviour. These symptoms disappeared completely after 4 weeks of treatment with creatine after which the patient regained all his previous mental abilites. Brain (white matter) proton magnetic resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in relation to choline-containing compounds (Cho). Urinary creatinine excretion as an indicator of the muscle and brain creatine pool increased upon short-term (12 days) high-dosage creatine supplementation (20 g per day) while plasma creatinine concentrations as possible indicators both of increasing creatine pool and of renal insufficiency increased during the course (28 months) of low-dosage creatine supplementation (5 g per day). Deterioration of renal function was finally indicated by urea retention and by impairment of renal creatinine clearance. These observations suggest that creatine supplementation may have a neuroprotective effect in patients with MELAS and episodes of acute mental deterioration. Adverse effects of creatine supplementation on renal function must be considered especially in patients with preexisting nephropathy.
 ...
PMID:Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy. 1220 Jul 46

Primidone is used alone or with other anticonvulsants in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy. Primidone was nominated by the National Cancer Institute for 2-year toxicology and carcinogenicity studies due to its human use as an anticonvulsant. Male and female F344/N rats and B6C3F1 mice received primidone (greater than 99% pure) in feed for 14 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 14-DAY STUDY IN RATS: Five male and five female rats were exposed to 0, 1,250, 2,500, 5,000, 10,000 or 20,000 ppm primidone (equivalent to average daily doses of approximately 120, 240, 500, 970, or 1,100 mg primidone/kg body weight to males and 120, 240, 500, or 900 mg/kg to females) in feed for 14 days. All 20,000 ppm females died before the end of the study as did one 10,000 ppm male and two 20,000 ppm males. The mean body weights of 10,000 ppm males and females and 20,000 ppm males were significantly less than those of the controls. Feed consumption by all exposed rats was generally similar to that by the controls. Males and females in the 10,000 and 20,000 ppm groups were observed to have eye discharge, ataxia, and abnormal posture and were thin and lethargic. 14-DAY STUDY IN MICE: Five male and five female mice were exposed to 0, 625, 1,250, 2,500, 5,000 or 10,000 ppm primidone (equivalent to average daily doses of approximately 100, 200, 400, or 800 mg/kg body weight to males and 100, 250, 500, or 900 mg/kg to females) in feed for 14 days. All mice in the 10,000 ppm groups and one male and one female mouse in the 5,000 ppm groups died on day 3 of the study. The mean body weights of mice in the 625, 1,250, 2,500, and 5,000 ppm groups were similar to those of the controls. Feed consumption by all exposed mice was generally similar to that by the controls. Males and females in the 10,000 ppm groups were observed to have abnormal posture, ataxia, and lethargy. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 0, 300, 600, 1,300, 2,500, or 5,000 ppm primidone (equivalent to average daily doses of approximately 20, 40, 100, 200, or 400 mg/kg) in feed for 14 weeks. All rats survived to the end of the study. The mean body weights of male and female rats in the 2,500 and 5,000 ppm groups were significantly less than those of the controls. Feed consumption by all exposed rats was generally similar to that by the controls. A minimal to mild exposure-related thrombocytosis occurred on day 22 and at week 14 in all exposed groups of male rats and in females in the 1,300 ppm or greater groups. A minimal decrease in hemoglobin concentration occurred in 2,500 and 5,000 ppm male and female rats on day 22 and at week 14. The incidences of centrilobular hepatocyte hypertrophy in male rats exposed to 600 ppm or greater and in female rats exposed to 1,300 ppm or greater were significantly greater than those in the controls. The severity of chronic nephropathy in male rats exposed to 1,300 ppm or greater increased with increasing exposure concentration. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 0, 300, 600, 1,300, 2,500, or 5,000 ppm primidone (equivalent to average daily doses of approximately 50, 100, 200, 400, or 1,000 mg/kg to males and 60, 120, 220, 440, or 1,100 mg/kg to females) in feed for 14 weeks. Three male and two female mice in the 5,000 ppm group died during week 1 of the study. The final mean body weights of all exposed groups were similar to those of the controls. Feed consumption by male mice in the 5,000 ppm group was slightly greater than that by the controls; this may have been due to feed spillage. Male and female mice in the 5,000 ppm groups were ataxic and lethargic. Compared to controls, the estrous cycle lengths of females exposed to 1,300, 2,500, or 5,000 ppm were significantly longer. The liver weights of male and female mice exposed to 600 po 600 ppm or greater were significantly greater than those of the controls. The incidences of centrilobular hepatocyte hypertrophy in all exposed males and in females exposed to 600 ppm or greater and the incidences of cytoplasmic alteration of the adrenal gland and hematopoietic cell proliferation of the spleen in 2,500 and 5,000 ppm males and in 5,000 ppm females were significantly greater than in the controls. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 0, 600, 1,300, or 2,500 ppm primidone (equivalent to average daily doses of approximately 25, 50, or 100 mg/kg) in feed for 2 years. Survival, Body Weights, and Feed Consumption Survival of the 1,300 and 2,500 ppm males was sig nificantly less than that of the controls. The mean body weights of males and females in the 2,500 ppm groups were less than those of the controls, beginning at week 29 for males and week 17 for females; the mean body weights of 1,300 ppm males and females were less than those of the controls during the second year of the study. Feed consumption by all exposed groups of rats was generally similar to that by the controls. Pathology Findings Male rats exposed to primidone had increased inci dences of thyroid gland follicular cell neoplasms (adenoma and/or carcinoma). All exposed groups of male rats had follicular cell adenomas or carcinomas (combined) at incidences above the historical control range, with the highest incidence in the 1,300 ppm group. Hepatocyte cytoplasmic vacuolation and centrilobular hypertrophy were associated with primidone exposure in male and female rats. These changes were more severe in females than in males and the incidences in all exposed groups of females were significantly greater than those in the controls. Females in the 2,500 ppm group had an increased incidence of hepatocellular eosinophilic foci. In 2,500 ppm males, the incidence of renal tubule hyperplasia was greater than that in the controls in the standard evaluation. Additional hyperplasias were found in the extended evaluation, and the incidences in exposed groups of males were significantly greater than that in the controls. In the extended evaluation, the incidence of renal tubule adenoma in 2,500 ppm males was significantly increased. The incidence of adenoma or carcinoma (combined) in 2,500 ppm males in the combined standard and extended evaluations were marginally increased over those in the controls. Male rats had an exposure-related increase in the severity of chronic nephropathy, which probably accounted for the reduced survival in the 1,300 and 2,500 ppm groups. The incidences of kidney cysts were increased in 1,300 and 2,500 ppm males. Hyperparathyroidism, secondary to the loss of renal function, was present in many exposed male rats. The incidences of parathyroid gland hyperplasia in all groups of exposed males were significantly greater than that in the controls. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to dietary levels of 0, 300, 600, or 1,300 ppm primidone (equivalent to average daily doses of approximately 30, 65, or 150 mg/kg to males and 25, 50, or 100 mg/kg to females) in feed for 2 years. Survival, Body Weights, Feed Consumption, and Clinical Findings Survival of the 1,300 ppm males was significantly less than that of the controls. During the second year of the study, the mean body weights of 1,300 ppm male and female mice were less than those of the controls. The final mean body weights of 600 ppm males and females were less than those of the controls. Feed consumption by all exposed groups of mice was similar to that by the controls. During the latter part of the study, a treatment-related increase in the number of animals with swelling of the abdominal area was observed; necropsy revealed that the swelling was due to liver nodules/masses. Pathology Findings The liver was a target organ in both male and female mice. The incidences and multiplicities of hepatocellular neoplasms (hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma) in all exposed groups of males and females (except hepatoblastoma in females) were significantly greater than those in the controls. The incidences of hepatocellular adenoma or carcinoma (combined) and hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma (combined) in all exposed groups exceeded the historical control ranges in 2-year NTP studies. The incidences of centrilobular hepatocyte hypertrophy were increased in exposed groups of males and females, and the severities increased with increasing exposure concentration. The incidences of cytoplasmic vacuolization were increased in all exposed groups of females and in 300 ppm males. Incidences of eosinophilic focus in all exposed groups of females were significantly greater than those in the controls. Proliferative changes occurred in the thyroid gland in an exposure-related manner in male and female mice. Incidences of follicular cell hyperplasia were increased in all exposed groups of males and in 600 and 1,300 ppm females, but incidences of follicular cell adenomas were increased only in male mice. GENETIC TOXICOLOGY: Primidone was mutagenic in Salmonella typhimurium strain TA1535 in the absence of S9 activation only; no mutagenicity was detected in strain TA98, TA100, or TA1537, with or without S9. Primidone did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. The single in vivo study with primidone, a mouse bone marrow micronucleus test, also gave negative results. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was equivocal evidence of carcinogenic activity of primidone in male F344/N rats based on a marginal increase in thyroid gland follicular cell neoplasms, primarily adenomas, and a marginal increase in renal tubule neoplasms. There was no evidence of carcinogenic activity of primidone in female F344/N rats exposed to 600, 1,300, or 2,500 ppm. There was clear evidence of carcinogenic activity of primidone in male B6C3F1 mice based on the increased incidences of hepatocellular neoplasms, and the increased incidence of thyroid gland follicular cell adenomas was also considered to be chemical related. There was clear evidence of carcinogenic activity of primidone in female B6C3F1 mice based on the increased incidences of hepatocellular neoplasms. Exposure of rats to primidone resulted in increased incidences of hepatocyte cytoplasmic vacuolization and centrilobular hypertrophy in males and females and eosinophilic foci in females. The increased severity of nephropathy and increased incidence of renal tubule hyperplasia in male rats were related to primidone exposure. Exposure of male mice to primidone resulted in hepatocyte centrilobular hypertrophy and thyroid gland follicular cell hyperplasia. Exposure of female mice to primidone resulted in hepatocyte centrilobular hypertrophy and cytoplasmic vacuolization, eosinophilic focus, and thyroid gland follicular cell hyperplasia. Synonyms: 5-Aethyl-5-phenyl-hexahydropyrimidin-4,6-dion; 2-deoxyphenobarbital; 2-desoxyphenobarbital; desoxyphenobarbitone; 5-ethyldihydro-5-phenyl-4,6 (1H,5H)-pyrimidinedione; 5-ethylhexahydro-4,6-dioxo-5-phenylphrimidine; 5-ethylhexahydro-5-phenylpyrimidine-4,6-dione; 5-ethyl-5-phenylhexahydropyrimidine-4,6-dione Trade names: Cyral; Hexadiona; Hexamidine; Lepimidin; Lepsiral; Majsolin; Midone; Milepsin; Misodine; Misolyne; Mizodin; Mizolin; Mylepsin; Mylepsinum; Mysedon; Mysoline; Prilepsin; Primacione; Primaclone; Primacone; Primakton; Primadon; Prysoline; Pyrimidone; ROE 101; Sertan
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Primidone (CAS No. 125-33-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1257 87

Long-term prognosis in dialysis is poor compared to that in healthy control persons. A worsening of the prognosis is noted especially for patients who at initiation of dialysis have congestive heart failure, ischemic heart disease, or left ventricular dysfunction or hypertrophy. This is the main reason that cardiovascular causes are the most common for morbidity in these patients. The weight obtained when normal urine output is present is the dry weight. With reduced ability to excrete the volume by the kidneys in end-stage renal disease (ESRD), the body will retain water and the patient will gain weight. This extra weight is due to volume overload. While volume overload may induce a rise in blood pressure, if the heart is in acceptable condition, a fast removal of fluid by ultrafiltration (UF) during dialysis may instead cause hypotension. Ultrafiltration failure in peritoneal dialysis (PD) patients may lead to successive water retention and overhydration with subsequent cardiac failure, while volume overload may occur over a few days in hemodialysis (HD) patients. Anemia or even too-high hematocrit may impair cardiac function further and worsen conditions caused by wrong dry weight. Thus, during long-term and sustained volume overload, left ventricular (LV) hypertrophy will occur in an eccentric manner. A sustained overload then may lead to cell death and LV dilatation and, eventually, systolic dysfunction. Once a severe left ventricular dilatation has developed, the blood pressure may decrease during volume overload. A worsened prognosis is seen if malnutrition and low albumin levels are present. Volume overload necessitates ultrafiltration to achieve dry weight. Thereby, volume contraction contributes to exaggerated stimulation of or response to activation of the RAS and alpha-adrenergic sympathetic systems. If ultrafiltration goes beyond these compensatory mechanisms, hypotension will occur and increase the risk for hypoperfusion of vital organs. Such episodes may cause cardiac morbidity, aspiration pneumonia, vascular access closure, or neurological complications (seizures, cerebral infarction), besides a more rapid lowering of residual renal function. Preventive measures are, first, finding the right dry weight; second, minimizing interdialytic weight gain; third, optimizing the target for hemoglobin (110-120 g/l); fourth, lowering dialysate calcium (1.25 mmol/l); and fifth, eventually using higher dialysate potassium if long dialyses are performed.
 ...
PMID:Ultrafiltration and dry weight-what are the cardiovascular effects? 1266 7


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