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Biomedical subjects

M B Tennison

Publications and source records attributed to M B Tennison.

At least 19 recordsLinked to original sources
PubMed1999

When to start and stop anticonvulsant therapy in children.

A large body of evidence has accrued in recent years, allowing a more precise estimate of the risk of seizure recurrence for children with new-onset seizures and for children who stop therapy once they are seizure-free. The primary goal for children with epilepsy is not solely freedom from seizures, but an optimal quality of life. Unless the physician can predict a recurrence risk at the extremes (0% or 100%), the nonmedical factors that affect quality of life will usually dominate the family's decision making. Together, the physician and family should weigh the risks and benefits of treatment against the risks and benefits of withholding or stopping therapy. Antiepileptic drug treatment should be withheld from most children until they have had a second seizure. Most children who receive antiepileptic drug treatment should attempt to taper their medications after 2 years without seizures.

Anticonvulsants↗
PubMed1997

HIV-infected children with hemophilia: one- and two-year follow-up of neuropsychological functioning.

This report describes the absence of neuropsychologic change observed over a 2-year period for 25 HIV-seropositive (HIV+) children and adolescents with hemophilia and 33 HIV-seronegative (HIV-) controls. Efforts were made to match the groups on the basis of chronological age, race, and hemophilia severity. The baseline evaluation included blinded neuropsychologic measurement of motor, attention, language, visual processing, memory, and general intelligence. HIV+ and HIV-group means did not differ at baseline on any neuropsychologic domain, and this trend continued at the 2-year follow-up. Mixed models analyses did not indicate that the HIV+ group performed more poorly than the HIV- group on any of the neuropsychological domains, nor did they show different patterns of change over time on these variables for the HIV+ group. Consistent with emergent findings, it continues to be premature to attribute subtle neuropsychologic deficits in seropositive children with hemophilia directly to the central nervous system (CNS) effects of HIV infection.

AIDS Dementia Complex↗
PubMed1996

Similarities of EEG and seizures in del(1q) and benign rolandic epilepsy.

We studied the seizure disorders manifested by three previously reported children with "de novo" terminal deletions of the long arm of chromosome 1 (46,XX,del(1)(q43)) and similar clinical phenotypes. In late infancy, two of these children developed partial seizures characterized by tonic-clonic movements of the ipsilateral face and arm with occasional involvement of the leg. In both children, the seizure frequency decreased with increasing age. Electroencephalograms of these two children demonstrated centrotemporal spike discharges morphologically similar to rolandic spikes. Although these cases present significant similarities to benign rolandic epilepsy, they also express many manifestations not detected in benign rolandic epilepsy that may reflect the extensive deletion of chromosome 1. Based on the seizure semiology and centrotemporal epileptiform discharges, we suggest that the distal portion of the long arm of chromosome 1 is a potential site for a candidate gene for benign rolandic epilepsy.

Age Factors↗
PubMed1994

Fragile X phenotype in a patient with a large de novo deletion in Xq27-q28.

A 2-year-old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27-q28 including deletion of FMR-1. Molecular analysis of the patient was recently described in Tarleton et al. [1993: Hum Mol Genet 2(11): 1973-1974] and the deletion was estimated to be at least 3 megabases (Mb). His mother had 2 FMR-1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a de novo event. The patient does not appear to have clinical or laboratory findings other than those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies.

Chromosome Fragility↗
PubMed1993

Neuropsychologic functioning of human immunodeficiency virus-infected children with hemophilia.

Efforts to detect subtle but objective neuropsychologic deficits could clarify the early involvement of the central nervous system and the progression of human immunodeficiency virus (HIV) infection in older children and young adolescents. Baseline examinations of 63 children and adolescents with hemophilia were conducted by examiners unaware of HIV status or staging or of our study's major hypotheses. They measured six domains of neuropsychologic functioning (motor, language, memory, attention, visual processing, and problem solving), and no differences between groups of similar age, race, and socioeconomic status defined by HIV seropositivity (n = 25) and HIV seronegativity (n = 38) were revealed. A high incidence of subtle neuropsychologic deficits relative to (1) age norms and (2) individual cognitive potential was found on measures of motor performance, attention, and speeded visual processing within both infected and uninfected groups. On the basis of these baseline data, it seems premature to attribute early, subtle neuropsychologic deficits in seropositive children with hemophilia to the central nervous system effects of HIV infection.

Adolescent↗
PubMed1991

Intraindividual variability of carbamazepine, phenobarbital, and phenytoin concentrations in saliva.

The intraindividual variability of salivary carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT) concentrations was studied in six healthy male volunteers. During three consecutive 1-week phases, subjects took one of the antiepileptic drugs (AED) for 5 days. Nine saliva and nine blood samples were collected simultaneously over the last 4 days of each phase. Salivary, unbound serum, and total serum CBZ, PB, and PHT concentrations were determined by fluorescence polarization immunoassay. Individual mean saliva (Cs)/total serum (Ct), unbound serum (Cu)/Ct, and Cs/Cu concentration ratios for CBZ, PB, and PHT were similar to those reported previously. The intraindividual mean (+/- SD) coefficients of variation (%) of the Cs/Ct, Cu/Ct, and Cs/Cu ratios for CBZ were 4.8 +/- 2.2%, 4.4 +/- 1.8%, and 5.0 +/- 1.9%, respectively; for PB they were 5.1 +/- 0.8%, 3.6 +/- 0.9%, and 6.4 +/- 1.0%, respectively; and for PHT they were 7.4 +/- 3.1%, 5.5 +/- 1.2%, and 8.3 +/- 3.2%, respectively. The mean Cs/Ct and Cu/Ct ratios for CBZ and PHT were not significantly different, but they were different for PB (p = 0.01). However, the range of individual coefficients of variation of the Cs/Ct ratio for PB was 4.0-6.2%, which is acceptable for clinical monitoring. We conclude that the intraindividual variability of CBZ, PB, and PHT concentrations in saliva, based upon the saliva/serum concentration ratios of each AED, is not a factor that should dissuade clinicians from using saliva for the therapeutic monitoring of these agents.

Adult↗
PubMed1991

Methsuximide for intractable childhood seizures.

Methsuximide was added to the therapeutic regimens of 25 children with intractable epilepsy. In 15 patients the drug was well tolerated and resulted in a 50% or greater reduction in seizure frequency. No serious or irreversible adverse effects were seen. Methsuximide is frequently overlooked and may be an effective adjunctive antiepileptic for children with intractable seizures.

Adolescent↗
PubMed1990

Evaluation of the Ames Seralyzer for the determination of carbamazepine, phenobarbital, and phenytoin concentrations in saliva.

The performance of the dry-phase apoenzyme reactivation immunoassay system (ARIS) for the measurement of carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT) concentrations in saliva was compared with fluorescence polarization immunoassay (FPIA). Blood and saliva samples were collected from 163 adult and pediatric epilepsy patients, then analyzed using both methods. Regressions between ARIS saliva CBZ, PB, and PHT concentrations, and FPIA unbound and total serum concentrations were highly correlated, but the ARIS technique was somewhat less precise than the FPIA. Valproic acid co-medication did not affect the relationships between ARIS and FPIA saliva concentrations and unbound serum concentrations of PHT, but did disrupt the relationship between ARIS and FPIA saliva PHT and total serum PHT. The sensitivity, specificity, predicted value positive (PV+) of a therapeutic concentration, and predicted value negative (PV-) of a concentration outside the therapeutic range for the ARIS saliva technique compared very well with FPIA for CBZ, PB, and PHT. The ARIS technique for CBZ, PB, and PHT saliva determination provides acceptable accuracy, precision, and sensitivity for therapeutic monitoring. In practice, the benefits of the ARIS saliva technique, including ease of collection, safety, patient/parent acceptance, and short analysis time, are striking.

Carbamazepine↗
PubMed1990

Rapid loading of critically ill patients with carbamazepine suspension.

To determine the rate and factors that affect carbamazepine absorption, six patients being treated in the pediatric intensive care unit for frequent seizures received loading doses (7.4 to 10.4 mg/kg) of carbamazepine suspension by either nasogastric or nasoduodenal tube. Carbamazepine serum concentrations were determined 15, 30, 60, 120, and 480 minutes after administration by fluorescence polarization immunoassay. One patient who had an ileus did not attain therapeutic concentrations (greater than 4.0 mg/L). The other five patients with normal gastrointestinal function achieved mean serum concentrations at 1 hour and 2 hours of 4.3 mg/L and 7.3 mg/L, respectively. Delayed gastric emptying and concurrent enteral feedings appear to slow the absorption of carbamazepine. No adverse effects were observed. Rapid loading with carbamazepine suspension appears to be a useful alternative for the management of critically ill pediatric patients who are experienced frequent seizures.

Adolescent↗
PubMed1989

Erythromycin effects on multiple-dose carbamazepine kinetics.

To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.

Absorption↗
PubMed1989

Determination of N-desmethylmethsuximide serum concentrations using enzyme-multiplied and fluorescence polarization immunoassays.

N-Desmethylmethsuximide (NDM), the active metabolite of the antiepileptic agent methsuximide, has been analyzed by gas-liquid chromatography and high-performance liquid chromatography (HPLC) in the past. This study compares methods using two commercially available immunoassays for ethosuximide, the enzyme multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (FPIA), with an HPLC method for the measurement of NDM concentrations in serum. Within-day precision studies, utilizing low therapeutic (15.0 mg/L) and toxic (45.0 mg/L) NDM concentrations (n = 20), resulted in coefficients of variation (CVs) of 4.6 and 4.2%, respectively, for EMIT and 5.4 and 3.2%, respectively, for FPIA. Day-to-day precision studies (n = 10) resulted in CVs of 7.6 and 5.5%, respectively, for EMIT and 3.5 and 2.4%, respectively, for FPIA. No interference was observed from toxic concentrations of acetaminophen, caffeine, carbamazepine, methsuximide, phenobarbital, phensuximide, phenytoin, primidone, salicylate, and valproic acid in the EMIT and FPIA procedures. There was good linear correlation between EMIT and HPLC NDM determinations of 50 patient samples (r = 0.970; y = 0.96 x + 0.03), and a similar correlation between FPIA and HPLC NDM determinations in 48 patient samples (r = 0.975; y = 0.91 x + 1.24). Using ethosuximide reagents, both EMIT and FPIA systems can be adapted to reliably measure NDM serum concentrations.

Chromatography, High Pressure Liquid↗
PubMed1984

Reversible visual evoked potential abnormalities in vitamin E deficiency.

A patient with cystic fibrosis and cirrhosis developed a progressive neurological syndrome associated with ataxia, proximal weakness, and ophthalmoplegia. Profound deficiencies of vitamins A, D, and E were present. Visual acuity and results of retinal funduscopy were normal. The pattern reversal visual evoked potential was initially abnormal (P100 latency, 136 and 130 ms from left and right eyes, respectively) but became normal (less than 3 standard deviations from mean control P100 latency) over a two-month period when vitamin E was administered. This case documents a potentially reversible visual evoked potential abnormality in a visually asymptomatic patient with vitamin E deficiency.

Adult↗
PubMedDate not supplied

Möbius syndrome in infant exposed to cocaine in utero.

The pathophysiology of Möbius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome. An infant is reported who was born with Möbius syndrome after a pregnancy complicated by heavy maternal use of cocaine and alcohol. We speculate that cocaine-induced vasoconstriction at a critical time of cerebrovascular development produced a vascular disruption sequence leading to the Möbius syndrome.

Adult↗
PubMedDate not supplied

Valproate metabolites and hepatotoxicity in an epileptic population.

Idiosyncratic hepatotoxicity, although rare, is of major concern when one is treating patients with valproate (VPA). Several clinical criteria are associated with an increased risk of developing this complication, but more specific predictors are needed. It has been postulated that 4-en-VPA or one of its further metabolites may be responsible for the hepatic toxicity and that under certain conditions the metabolism of VPA is shifted to this product. We postulated that measurement of serum concentrations of 4-en-VPA or another metabolite might be a simple technique that would be predictive of risk for developing idiosyncratic hepatotoxicity. Because this complication is rare, we chose to analyze our data by a multiple linear regression model, exploring associations between VPA or three of its metabolites and clinical risk factors for hepatotoxicity. 4-en-VPA correlated with older age and absence of encephalopathy. 4-en-VPA was only seen in patients receiving polytherapy; all patients were also receiving CBZ. 2-en-VPA correlated with poor nutritional status. We conclude that routine measurement of serum 4-en-VPA is unlikely to be a useful predictor of risk for developing fatal hepatotoxicity. Serum concentrations of 4-en-VPA may not reflect presence or effects in the liver as it may be metabolized to further intermediates or be bound to tissue. Thus, serum levels of 4-en-VPA do not reflect its important role in the pathogenesis of hepatotoxicity. This metabolite was detected only in patients receiving polytherapy, a potent risk factor for developing this rare complication.

Adolescent↗
PubMedDate not supplied

Effects of enteral tube feeding on the absorption and pharmacokinetic profile of carbamazepine suspension.

In a randomized, two-period crossover clinical study, eight normal male volunteers received two separate 500-mg doses of carbamazepine (CBZ) suspension 1 week apart. One dose was administered orally after an overnight fast, and the other was administered by nasogastric feeding tube during a continuous enteral feeding infusion. Serial serum CBZ concentrations were determined by high-performance liquid chromatography (HPLC) to assess the effects of the enteral feeding on CBZ absorption. Noncompartmental methods were used to estimate pharmacokinetic data. One volunteer experienced a mild hypersensitivity reaction after his first CBZ dose and was withdrawn from the study. The other subjects tolerated both doses very well, although most experienced mild drowsiness or lightheadedness. Serum CBZ concentrations were lower during enteral feeding administration, but the differences were statistically significant only at 8 h (p = 0.044). Changes in pharmacokinetic data were not significant, although the decrease in maximum serum concentration approached significance (p = 0.052). The relative bioavailability of CBZ suspension with enteral feeding administration was 90.1% of that during fasting. There was a strong correlation between CBZ dose (mg/kg) and Cmax after oral administration (r = 0.97, Y = 1.88X - 4.49, p less than 0.001) but not during enteral feeding administration. Although absorption of CBZ suspension was generally slower and slightly diminished during nasogastric feeding, this interaction may lessen unwanted side effects.

Absorption↗