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)

We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich-Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically.
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PMID:Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats. 232 2

The central nervous system (CNS) sensitivity to the hypnotic (general anesthetic) action of phenobarbital and to the neurotoxic (convulsive) action of theophylline is greater in rats with acute renal failure than in normal animals, consistent with clinical observations. In the case of phenobarbital, this increased sensitivity can be produced in normal rats by infusion of a solution of the lyophilized dialysate of serum from rats with renal failure. It was hypothesized that the relevant constituent(s) of this dialysate may circulate between the blood and the intestinal lumen and that it (they) can be adsorbed by orally administered activated charcoal and thereby removed from the body. If so, treatment of renal failure rats with activated charcoal should partly reverse the increased CNS sensitivity to phenobarbital and to other drugs similarly affected. Accordingly, rats with renal failure produced by bilateral ligation of ureters were given an aqueous suspension of activated charcoal, about 1 g per kg body weight, orally every 8 hr for six doses. Uremic controls received equal volumes of water. About 2 hr after the last dose, the animals were infused i.v. with phenobarbital to onset of loss of righting reflex or with theophylline to onset of maximal seizures. In the phenobarbital study, charcoal treatment partly reversed the hypothermia associated with renal failure and caused a reduction of creatinine and total bilirubin concentrations in serum. The cerebrospinal fluid (CSF) concentration of phenobarbital at onset of loss of the righting reflex was significantly higher in charcoal treated rats than in their controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of drug action in disease states. XXXIX. Effect of orally administered activated charcoal on the hypnotic activity of phenobarbital and the neurotoxicity of theophylline administered intravenously to rats with renal failure. 233 96

Ifosfamide/mesna was given to 97 patients who had malignant solid tumors diagnosed before they were 21 years of age. Patients received 1.6 g/m2 ifosfamide daily x 5, given i.v. over 15 min, followed by 400 mg/m2 i.v. mesna at 15 min and 4 and 6 h after ifosfamide. Responses were noted in patients with osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma and other soft-tissue sarcomas, rhabdoid tumor, neuroblastoma, Wilms' tumor, primitive neuroectodermal tumor, retinoblastoma, germ-cell tumors, and B-cell lymphoma. Toxicity included mild to moderate nausea and vomiting, transient, reversible myelosuppression, transient elevations of serum blood urea nitrogen (BUN) and creatinine and liver enzymes, infections, and self-limiting neurotoxicity characterized by changes in mental status, motor dysfunction, cranial nerve palsy, cerebellar dysfunction, and seizures. Neurotoxic symptoms were generally seen in patients who had previously received cisplatin. Ifosfamide is an important alkylating agent that should be combined with other agents in phase II and III trials. Alternate dose schedules should also be investigated.
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PMID:Ifosfamide in pediatric malignant solid tumors. 250 57

Twenty patients treated with human recombinant erythropoietin (EPO) for 9 months were studied. The patients were randomly allocated to high flux (HF) or conventional dialysis (CD). Patients on HF used the F-60 or F-80 dialyzer, with a polysulfone membrane; QB: 470 ml/min; QD: 800 ml/min; t: 127 min; Kt/V: 1.01. Conventional dialysis patients used regenerated cellulosic membranes; QB: 297 ml/min; QD: 500 ml/min; t: 193 min; Kt/V: 1.05. Mean dose of EPO was 103 U/kg for HF patients and 112.4 U/kg for patients on CD. At 9 months, no significant differences were observed in HCT (HF 33.6% vs. CD 33.2%), BUN, serum creatinine, potassium, or phosphorus. Hemoconcentration during dialysis was 12% for HF and 17% for CD. Urea clearance decreased 7% for HF and 9% for CD, while clearance of creatinine, potassium, and phosphorus decreased between 14 and 18% with both treatments. Heparin requirements increased 10% in HF and 16% in CD. Hypertension was similar in both groups. One HF patient withdrew from the study because of hypertension and one HF patient had seizures related to hypertension. Vascular access clotting or hospitalizations were no different. High flux dialysis patients on EPO over a 9 month period did not have any catastrophic complications when HCT was maintained between 30 and 35%.
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PMID:Are high flux dialysis and erythropoietin treatment in a collision course? 268 11

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach. 270 9

The systemic manifestations of "asphyxia" were evaluated prospectively in 35 consecutively intubated term newborn infants. The following systemic organ injuries were identified most often: (1) renal, ie, oliguria less than 1 mL/kg per hour for at lest 24 hours (40%), an elevated urinary beta-2-microglobulin concentration (57%), azotemia (11%), and an elevated serum creatinine level (17%); (2) central nervous system, ie, hypoxic-ischemic encephalopathy (including seizures) (31%) or an abnormal cranial ultrasound scan, ie, diffuse parenchymal echogenicity, slitlike ventricles, and poor visualization of the sulci, and/or intracranial hemorrhage (26%); (3) cardiovascular, ie, an abnormal echocardiogram (25%) or abnormal electrocardiogram (11%); (4) pulmonary complications, including persistent pulmonary hypertension (23%); and (5) gastrointestinal complications, which were rare. Traditional markers of fetal distress were not related to the frequency and/or distribution of systemic organ injury. An important implication of this study relates to the recognition of the extent and distribution of organ injury in the "asphyxiated" infant.
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PMID:Acute systemic organ injury in term infants after asphyxia. 271 98

The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.
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PMID:Central nervous system toxicity of cyclosporine in a rat model. 275 57

A 60-year-old woman who for many years had been taking salicylate-containing tablets for headaches, was admitted to hospital, in a somnolent state, because of increasing weakness, tiredness, memory and speech disorders, and tinnitus. Laboratory tests revealed a decompensated metabolic acidosis (pH 7.25), renal insufficiency (creatinine 2.3 mg/dl) and a decreased Quick value (63%). Whole-blood acetylsalicylic acid concentration was markedly elevated to 330 micrograms/ml. After treatment of the acidosis with bicarbonate and forced diuresis she at first regained consciousness, but clouding of consciousness again occurred eight hours later progressing to coma with unequal pupils and seizure potentials in the electroencephalogram. Status epilepticus without motor component was diagnosed, perhaps the result of a dysequilibrium of acid-base balance between blood and cerebrospinal fluid. The signs and symptoms were quickly reversed under treatment with clonazepam.
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PMID:[Cerebral complications in chronic acetylsalicylic acid poisoning]. 291 58

Blood pressure, which ist the product of cardiac output and peripheral vascular resistance is regulated by a complex feedback mechanism involving the sympathetic and parasympathetic systems and hormones. An acute disturbance of regulation may lead to a life-threatening increase in blood pressure. Diagnosis is based upon a careful measurement of blood pressure, which must be performed under internationally standardized conditions. Hypertensive crisis refers to a rapid blood pressure increase greater than 30 mmHg above the age-related 95th percentile. The main causes of hypertension in childhood are renal diseases, which may be aggravated by additional conditions either by the clinician himself (e.g. cyclosporin, steroids) or by the patient (lack of compliance). Crisis affects the brain (hypertensive encephalopathy), the heart (left ventricular insufficiency), the retina (visual disturbances) and the mucous membranes (epistaxis). Hypertensive encephalopathy is induced by a break-through of the autoregulation of brain flow, leading to hyperperfusion and, thus to cerebral oedema. The clinical manifestations are characterized by restlessness, severe and diffuse headache, vomiting, nystagmus, impaired vision, dizziness, paraesthesia, seizures and palsies, which may lead - if untreated - to coma and death. The course is usually prolonged and reversible by adequate treatment. The morphological consequences are purpura cerebri, fresh retinal haemorrhages and papillary oedema, apart from left ventricular dilatation and hypertrophy. The diagnostic procedure rests on the quick realization of essential anamnestic (blood pressure, renal disease, drugs), clinical (oedema, cardiac action, central nervous system, fundus) and laboratory parameters (serum creatinine, electrolytes, glucose, blood count, urine). Treatment should start before the manifestation of clinical signs (hypertensive emergency) with rapidly acting antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The hypertensive crisis in childhood]. 305 87

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.
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PMID:Phase II trial of ifosfamide in children with malignant solid tumors. 310 34


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