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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seizures are common in patients infected with human immunodeficiency virus (HIV). Phenytoin and valproic acid are common anticonvulsants, and both drugs are strongly bound to serum albumin. Because patients infected with HIV are often on polytherapy, using homeopathic medicines, and may also have hypoalbuminemia, elevated free drug concentrations may occur in these patients. The authors prepared one serum pool from patients infected with HIV but receiving no bactrim and the other pool from HIV patients receiving bactrim. They supplemented both HIV pools and normal pool (diluted with 0.9% saline to mimic albumin concentration of HIV pools) with a known concentration of phenytoin or valproic acid. After incubation at 37 degrees C for 3 hours, they measured free phenytoin and free valproic acid concentrations in the protein free ultrafiltrates using fluorescence polarization immunoassays. The total drug concentrations in original sera were measured by microparticle enzyme immunoassays. None of the patients had any significant liver or renal disease. The aliquots of HIV pools and normal pool were supplemented with the same concentration of phenytoin or valproic acid. The concentration of free phenytoin and free valproic acid were significantly elevated in patients with HIV (mean = 2.52, SD = 0.11 micrograms/ml for phenytoin; mean = 41.5, SD = 1.5 micrograms/ml for valproate) compared to controls (mean = 1.50, SD = 0.0 7 micrograms/ml for phenytoin; mean = 19.9, SD = 0.5 micrograms/ml for valproate). The concentrations of both free phenytoin and valproic acid were further elevated in patients prepared in the HIV pool who were receiving bactrim (mean = 2.81, SD = 0.09 micrograms/ml for phenytoin; mean = 44.0, SD = 1.1 micrograms/ml for valproate), but when normal serum pool was supplemented with 4.4 mg/dl of bactrim (concentration of bactrim in HIV pool) and supplemented with the same concentration of phenytoin or valproic acid, the observed free concentrations were much lower (mean = 1.65, SD = 0.05 micrograms/ml for phenytoin; mean = 26.1, SD = 1.4 micrograms/ml for valproate). This indicates that hypoalbuminemia and bactrim concentrations do not account for the observed free drug concentrations in patients with HIV. The authors also observed elevated free phenytoin and valproic acid in sera from three individual patients with AIDS compared to normals (normal serum diluted with 0.9% saline to mimic the albumin concentration of serum collected from a patient with HIV and then both specimens supplemented with the same concentration of phenytoin or valproic acid.
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PMID:Elevated free phenytoin and free valproic acid concentrations in sera of patients infected with human immunodeficiency virus. 948 57

To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.
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PMID:Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group. 955 72

We conducted a prospective cohort study to detect any relationships between specific clinical features and laboratory indices at initiation of hemodialysis and long-term survival. One hundred and thirty-nine consecutive patients with chronic renal failure hospitalized to start maintenance hemodialysis between January 1990 and December 1994 were enrolled, and follow-up was completed through December 1995. At baseline, subjects were assigned to one of five groups based on their major indication for initiation of hemodialysis. The indications were: (a) nausea and vomiting; (b) severe weakness; (c) no major symptom (dialysis started because of 'high' serum creatinine and blood urea nitrogen concentrations); (d) volume overload, and (e) miscellaneous (angina, pericarditis, seizure, pruritus, and hyperkalemia). Blood urea nitrogen, serum creatinine and serum albumin concentrations were measured once before the first dialysis. The main outcome measure was death. The 139 study subjects included 77 women and 62 men comprising 116 Blacks (83%), 15 Hispanics (11%), and 8 Whites (6%) of mean age 54 +/- 15 years. Mean length of follow-up was 39 months. At baseline, mean blood urea nitrogen concentration was 121 +/- 38 mg/dl, mean serum creatinine concentration was 12.6 +/- 5.2 mg/dl, and mean serum albumin concentration was 3.5 +/- 0.62 g/dl. Forty-two subjects (30%) died during follow-up. Cox regression analysis showed that there was no significant association between mortality and any of the indicators evaluated (indication for initiation of dialysis (p = 0.2), serum creatinine concentration (< 10 vs. > or = 10 mg/dl) (p = 0.8), blood ure nitrogen concentration (< 100 vs. > or = 100 mg/dl) (p = 0.68) and serum albumin concentration (< 4 vs. > or = 4 g/dl) (p = 0.62). All analyses included adjustment for age and diabetes. We conclude that in patients with chronic renal failure, the clinical features and laboratory indices used as guidelines for initiation of renal replacement therapy do not correlate with survival. Objective parameters that will permit initiation of dialysis at a time that will maximize survival in patients with chronic renal failure are needed.
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PMID:Timing of initiation of uremia therapy and survival in patients with progressive renal disease. 962 34

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacterial meningitis. The present study evaluates concentrations in ventricular cerebrospinal fluid (CSF) in the absence of pronounced meningeal inflammation. Patients with occlusive hydrocephalus caused by cerebrovascular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 30 min. Serum and CSF were drawn repeatedly and analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations in serum were 84.7 +/- 23.7 microg/ml. A CSF maximum (CmaxCSF) of 0.63 +/- 0.50 microg/ml (mean +/- standard deviation) was observed 4.1 +/- 2.6 h after the end of the infusion. CmaxCSF and the area under the curve for CSF (AUCCSF) depended on the AUC for serum (AUCS), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slower than from serum (half-life at beta phase [t1/2beta] of 7.36 +/- 2.89 h in CSF versus t1/2beta of 1.69 +/- 0.60 h in serum). The AUCCSF/AUCS ratio for meropenem, as a measure of overall CSF penetration, was 0.047 +/- 0.022. The AUCCSF/AUCS ratio for meropenem was similar to that for other beta-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular CSF observed in this study are high enough to kill fully susceptible pathogens. They may not be sufficient to kill bacteria with a reduced sensitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococci and Pseudomonas aeruginosa.
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PMID:Disposition and elimination of meropenem in cerebrospinal fluid of hydrocephalic patients with external ventriculostomy. 968 99

Adenosine, an endogenous inhibitory neuromodulator in the central nervous system, exerts anticonvulsant activity that is largely based on the inhibition of the release of excitatory amino acids. As a novel approach to treat pharmacoresistant partial epilepsies, the grafting of adenosine-releasing cells is foreseen to provide a local and sustained source of adenosine. The feasibility of this cell-based therapy was investigated in the present study by the intraventricular implantation of synthetic polymers that release adenosine. Kindled rats with a ventricular implant of an adenosine-releasing polymer showed a profound reduction of seizure activity. This was demonstrated not only by a 75% reduction of grade 5 seizures but also by a reduction of the amplitude and duration of afterdischarges in electroencephalographic (EEG) recordings. Kindled control rats that were implanted with bovine serum albumin (BSA)-containing polymers or were sham operated, continued to show their presurgery seizure pattern. Adenosine displayed antiepileptic activity when released in an amount of 20-50 ng per day. This finding sets the target for the required amount of adenosine to be released from future adenosine-releasing cells for antiepileptic therapy. The present results clearly support the feasibility of a novel therapy for epilepsy based on adenosine-releasing cells.
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PMID:Seizure suppression in kindled rats by intraventricular grafting of an adenosine releasing synthetic polymer. 1063 Feb 1

In a recent study, we reported that a restriction fragment length polymorphism associated with the alpha4 nicotinic receptor gene (Chrna4) may play a role in regulating differential sensitivity of LS and SS mouse lines to the seizure-inducing effects of nicotine. Since the alpha4 subunit (CHRNA4) is often found as a heteromer with the beta2 subunit (CHRNB2), alpha4 and beta2 cDNAs from the LS and SS mice were cloned and sequenced. A polymorphism in the coding portion of the alpha4 gene was found (1587A to G) which should result in a threonine/alanine substitution at position 529 (T529A). The LS and SS beta2 nicotinic receptor subunit cDNAs were identical. The potential consequences of the alpha4 polymorphism were evaluated using an ion (86Rb+) flux assay that likely measures the function of alpha4beta2-type receptors. LS-SS differences in maximal nicotine-stimulated ion flux were seen when bovine serum albumin (BSA) was not included but this difference was not seen when BSA was included in the perfusion buffer. Current evidence suggests that BSA may alter the ratio of nicotinic receptors that are in the ground state and desensitized forms. Thus, it may be that the Chrna4 T529A substitution leads to a difference in the ratio of the two receptor forms which then promotes differences in receptor function, as well as differential behavioural sensitivity to nicotine.
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PMID:Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux and alpha4 nicotinic receptor subunit cDNA sequence. 1143 11

Our objective was to investigate the relationship between phenytoin bioavailability, enteral feeding and serum albumin levels in patients admitted to neurology/neurosurgery ITU, via case studies of three patients. The research was performed at the Walton centre for Neurology and Neurosurgery NHS Trust, Liverpool, England, and our subjects consisted of three cases admitted to ITU (1 status epilepticus, 1 post-trauma and 1 post-subarachnoid haemorrhage (SAH)). Phenytoin levels were assessed in relation to the type of feeding and serum albumin levels. We found evidence of a complex relationship between phenytoin levels, enteral feeding and serum albumin in patients in the neuro ITU setting. We conclude that, in this setting the patient's phenytoin needs to be closely monitored and treated aggressively to maintain therapeutic levels. They should also be followed up during rehabilitation to avoid toxicity.
Seizure 2001 Jun
PMID:Problems with phenytoin administration in neurology/neurosurgery ITU patients receiving enteral feeding. 1146 22

An 80-year-old male without abnormal past medical history presented with coma, general seizures, and fever subsequent to abnormal behavior. The pressure of the cerebrospinal fluid(CSF) elevated(13.5-20.5 cm H2O), and CSF examination revealed pleocytosis with predominant mononuclear cells(80-879/mm3) and elevated protein level(32-130 mg/dl). DNAs of herpes simplex virus(HSV) type 1 and 2 in CSF were not confirmed by polymerase chain reaction method in the acute phase. The HSV(type 1) antibody(HSV-1 Ab) ratio of serum to CSF(= [serum HSV-1 Ab]/[CSF HSV-1 Ab]) was 0.98 and HSV-1 Ab index(= [CSF HSV-1 Ab]/[serum HSV-1 Ab] divided by [CSF albumin]/[serum albumin]) was 62.4. Initial fluid attenuated inversion recovery(FLAIR) (TR/TE/TI = 6,882/110/1,700 msec) axial magnetic resonance(MR) imaging showed hyperintensity in the subfrontal area, inferomedial portions of the temporal lobes, cingulate gyri, and insular cortices bilaterally. Meningoencephalitis caused by HSV-1 was diagnosed based on the values of HSV-1 Ab ratio of serum to CSF(less than 20), of HSV-1 Ab index(larger than 1.91), and the findings of MR imaging. Diffuse white matter lesions manifesting hyperintensity on FLAIR imaging in the bilateral frontal and temporal lobes close to the affected cortices developed approximately six weeks after the onset despite administration of antiviral agent and steroid. The lesion extensively involved the white matter of the bilateral frontal and temporal lobes finally. The initial value of myelin basic protein(MBP) in CSF was 0.9 ng/ml (normal value: less than 4 ng/ml). Subsequent measurement of MBP in CSF about two, six weeks, two, three, and six months after the onset showed a marked increase of 233.9 ng/ml followed by a gradual decrease of 25.4 ng/ml, 18.4 ng/ml, 7.4 ng/ml and 4.3 ng/ml, respectively. Therefore, demyelination of the lesion in the cerebral white matter was suggested by the chronological change in FLAIR imaging and MBP in CSF.
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PMID:[A high aged case of herpes simplex viral encephalitis associated with progressive cerebral white matter lesion]. 1157 20

We studied the effect of active immunization with glutamate-bovine serum albumin conjugate on acute generalized epileptiform activity evoked by single administration of corazol. Antibodies to glutamate produced an antiepileptic effect and elevated the threshold for clonic seizures and tonic phase of lethal seizures. In BALB/c mice this effect was more pronounced than in C57BL/6 mice.
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PMID:Elevation of corazol-induced seizure threshold after active immunization of mice of various genetic strains with glutamate-bovine serum albumin conjugate. 1466 87

The purpose of this study was to evaluate request forms of therapeutic drug monitoring of antiepileptic drugs for appropriateness criteria according to published data. Request forms received by the laboratory were sampled as all requests in one day per week on an alternating basis. Drugs monitored were phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ) and valproic acid (VPA). A total of 420 request forms were collected. Age, gender and weight were provided in 95.5%, 97.1% and 56.9% of request forms, respectively. The diagnosis, seizure type and the indication for therapeutic drug monitoring were provided in 81.6%, 3.2% and 55.5%, respectively. Sampling times were provided in 45% and were considered appropriate in 25.2% of the request forms. The indications for therapeutic drug-monitoring were considered appropriate in 28.6% of the request forms, and only 19.2% of these were appropriately sampled. Only 37.9% of all samples were drawn at steady-state. Serum albumin and creatinine concentrations were lacking in 93.6% and 53.3% of requests, respectively. The potential for drug-drug interactions was detected in 28.6% of all requests. Thus, the information needed for the proper interpretation of therapeutic drug monitoring results and that was provided in the request forms was surprisingly scarce. Most of the appropriateness criteria for therapeutic drug monitoring were not met.
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PMID:Appropriateness of requests for therapeutic drug monitoring of antiepileptic drugs: the experience in southwestern Saudi Arabia. 1507 78


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