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Biomedical subjects

J M Pellock

Publications and source records attributed to J M Pellock.

At least 73 records · Page 4Linked to original sources
PubMed1994

Standard approach to antiepileptic drug treatment in the United States.

Antiepileptic drugs (AEDs) are administered to patients for acute and long-term treatment of seizures. Most patients with acute convulsions receive intravenous (i.v.) benzodiazepine (BZD), frequently followed by i.v. loading with phenytoin (PHT), especially when seizures continue. For patients with absence status epilepticus, BZD is usually followed by ethosuximide (ESM) or valproate (VPA). The decision to continue AED therapy is based on the likelihood that seizures will continue or recur. Once epilepsy is diagnosed, long-term treatment with AEDs is recommended, beginning with monotherapy. Two studies sponsored by the U.S. Veterans Administration (VA), which compared the efficacy of carbamazepine (CBZ), PHT, phenobarbital (PB), primidone (PRM), and VPA, recommend that most adults with recurrent partial seizures receive either CBZ or PHT. The 1992 VA study suggests that VPA is equal to CBZ or PHT in efficacy when partial seizures become secondarily generalized. Primary generalized epilepsies are most frequently treated with VPA when combinations of generalized seizures exist. ESM is prescribed most often when typical childhood absence seizures exist alone. Although many authorities do not recommend long-term treatment of childhood febrile seizures, PB is administered by some when febrile seizures have complex symptomatology. In general, AED monotherapy is currently preferred, but those with more refractory epilepsy receive polytherapy. CBZ, PHT, PB, PRM, VPA, and ESM are the primary AEDs prescribed in the United States. PHT, followed by CBZ and VPA, is the most frequently prescribed AED as both new and total prescriptions. The introduction of felbamate, gabapentin,and lamotrigine may alter these patterns in the future.

Adult↗
PubMed1994

Flunarizine for treatment of partial seizures: results of a concentration-controlled trial.

The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).

Adolescent↗
PubMed1994

Status epilepticus in children: update and review.

This report presents a brief description and classification of status epilepticus. This neurologic emergency occurs more frequently in young children and elderly adults, although patients of all ages may experience prolonged seizures. The pathophysiology and prognosis of the disorder are presented, as well as a review of drugs commonly used for the treatment of convulsive status epilepticus. The morbidity and mortality of status epilepticus are significant and directly dependent upon prompt and appropriate medical therapy. Advances in understanding various aspects of status epilepticus may lead to improved outcome for affected patients.

Adolescent↗
PubMed1994

The clinical efficacy of lamotrigine as an antiepileptic drug.

Product license applications for lamotrigine have been filed or approved in more than 50 countries throughout the world. In preclinical models, this drug demonstrates activity against both maximal electroshock and pentylenetetrazol seizures. The primary action of lamotrigine is, most likely, blockade of sodium channels, with resultant inhibition of glutamate and aspartate release. As would be expected from this spectrum of activity, the drug has shown clinical efficacy in both partial and generalized seizures and in a variety of epilepsy syndromes. Particularly promising results have been demonstrated in difficult-to-control epilepsy syndromes with mixed seizures. Half-life of lamotrigine in adults receiving monotherapy is approximately 24 hours. Its half-life is decreased by approximately 50% when it is used in combination with enzyme-inducing antiepileptic drugs, such as phenobarbital, carbamazepine, and phenytoin; in contrast, valproate extends the half-life of lamotrigine by two- to three-fold. Its administration has no effect on the metabolism of other antiepileptic drugs, with the exception of a possible minor increase in the proportion of carbamazepine-10,11-epoxide. The usual maintenance dosage of lamotrigine is 200 to 500 mg daily given in two divided doses. In US open studies of adult patients with treatment-refractory partial epilepsy, increased seizure control was demonstrated with higher dosages. Extension studies have shown even better efficacy with daily doses of approximately 700 mg. Multiple studies and clinical usage have shown lamotrigine to be well tolerated, with patients reporting a sense of well-being during drug therapy. The most frequently reported adverse events are CNS-associated side effects and rash.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Characterization of seizures associated with biotinidase deficiency.

Biotinidase deficiency is an autosomal recessively inherited disorder that is often characterized by neurologic abnormalities. We reviewed the clinical features of 78 symptomatic children, 11 new patients and 67 previously reported cases, to determine the frequency, type, age at onset, and the responsiveness of seizures to antiepileptic drugs and biotin therapy. Forty-three of the 78 (55%) symptomatic children had seizures, and seizures were the presenting symptom in 38% of the enzyme-deficient patients and 70% of those who had had seizures at some time. EEGs were available for 21 of these children. Sixteen were abnormal. The initially abnormal EEGs in eight of 12 infants became normal or improved with biotin therapy, whereas four continued to be abnormal. In 21 (49%) patients, the seizures were not well controlled with antiepileptic drugs. Biotin therapy stopped the seizures within 24 hours in 12 of 16 (75%) of those whose seizures were uncontrolled by anticonvulsants (five children died prior to diagnosis). Although the metabolic and cutaneous abnormalities were corrected in the remaining four children, they continued to have neurologic abnormalities. Biotinidase deficiency and a trial of biotin (5 to 10 mg) should be considered in infants less than 1 year of age with poorly controlled seizures, and biotinidase deficiency should be included in the differential diagnosis of an infant or child with unexplained seizures.

Amidohydrolases↗
PubMed1993

Seizures and epilepsy in infancy and childhood.

The evaluation, diagnosis, and treatment of childhood epilepsy or isolated seizures deserve special consideration. Whenever possible, a working diagnosis of an epilepsy syndrome should be implemented early in the course of evaluation to help plan the necessary investigations and acute and chronic treatment. The plan will evolve over a number of years as the patient's syndrome is better defined. The overall neurologic status of the child and response to therapy are important prognostic factors. Treatment proceeds after balancing antiepileptic drug efficacy versus adverse drug effects. The length of treatment, discussion of prognosis, and likelihood for genetic transmission are all related to the proper diagnosis of epilepsy syndromes.

Adolescent↗
PubMed1992

Status epilepticus in children, adults, and the elderly.

Status epilepticus (SE) is a major neurological and medical emergency associated with a high morbidity and mortality. Retrospective and prospective studies from the Medical College of Virginia Epilepsy Research Center have been utilized to investigate several clinical and epidemiological factors associated with SE. Univariate and multivariate logistic regression analysis of predictive indicators in patients with SE indicated that seizure duration, certain specific etiologies, and age were predictors of mortality. Sex, race, and certain other etiologies were not found to be factors that significantly affect mortality. These findings demonstrate that specific indicators are important in predicting mortality in SE. Preliminary prospective epidemiological data from Richmond, Virginia suggested that more than 250,000 cases of SE may occur annually in the United States with a mortality greater than 55,000 individuals. Studies comparing community and university hospitals in Richmond indicate that the mortality and clinical variables associated with SE in these two hospital populations are essentially identical. Further investigations employing prospective population-based studies are essential in evaluating the epidemiology and mortality of SE.

Adolescent↗
PubMed1991

The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins.

Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.

Diseases in Twins↗
PubMed1990

The classification of childhood seizures and epilepsy syndromes.

The classification of seizures and the epileptic syndromes is particularly relevant to those who treat children, as most syndromes are age related, with onset between the neonatal and adolescent periods. Whereas seizures are characterized by ictal behavior and EEG findings, epilepsy syndromes are defined by seizure type, etiology, age of onset, natural history, possible genetic factors, and prognosis. Limitations exist, but attempts to use these classifications typically lead to a better understanding of the patient and allow for more precise evaluation and treatment.

Adolescent↗
PubMed1989

Efficacy and adverse effects of antiepileptic drugs.

One must balance carefully the need for seizure control and the resulting toxicity of the antiepileptic agent. The perfect antiepileptic drug is as yet unavailable; until it is, physicians must be aware of individual variations with regard to drug response and efficacy.

Abnormalities, Drug-Induced↗
PubMed1989

Usefulness of a single-dose prediction model for the determination of long-term maintenance therapy of valproic acid.

The single-dose prediction model (SDPM) of Slattery et al. has been shown accurately to predict short-term (3 to 7 days) steady-state valproic acid (VPA) concentrations in normal volunteers and in hospitalized patients receiving monotherapy. To assess the long-term usefulness of the SDPM in a real-life clinic setting, six ambulatory patients ranging in age from 2 to 8 years were studied. Blood samples were drawn at least 6 h after the initial dose but before the second dose of VPA, A steady-state trough concentration (Cminss) was measured 3 to 7 days after the initiation of therapy. Dosage adjustments and alterations in therapeutic regimen were allowed and another Cminss was measured after 1 to 12 months. Predicted Cminss values were calculated for both the short-term and long-term VPA regimens. Predictive performance analysis demonstrated that the SDPM was unbiased in predicting both short-term and long-term VPA Cminss values and precise in predicting only short-term VPA Cminss values. The SDPM is not a reliable predictor of long-term total VPA concentrations in seizure patients in an outpatient clinic setting.

Child↗
PubMed1988

Verification of the fetal valproate syndrome phenotype.

We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre- or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and/or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].

Abnormalities, Drug-Induced↗
PubMed1987

A comparative bioavailability study of carbamazepine tablets and a chewable tablet formulation.

Differences in product formulations have been shown to affect the therapeutic response by altering the relative bioavailability and pharmacokinetics of a drug. The relative bioavailability and pharmacokinetics of carbamazepine tablets (CBZ) and a chewable tablet formulation were evaluated in 10 normal healthy subjects (five men and five women). The study utilized a randomized, crossover design with a 4-week washout period between doses. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 14, 24, 30, 36, and 48 h following a 200-mg dose. Plasma samples were assayed by fluorescence polarization immunoassay. Ke, Cmax, Tmax, area under the curve (AUC), and relative bioavailability were estimated using traditional pharmacokinetic methods and compared by paired t test. A statistically significant higher Cmax (3.81 +/- 81 vs. 4.64 +/- .80 mg/L) was observed with the chewable tablet formulation but was not thought to be clinically relevant. No significant differences between formulations for Ke (0.022 +/- 0.007 vs. 0.025 +/- 0.008 h-1 h), Tmax (7.49 +/- 2.69 vs. 6.04 +/- 2.7 h), AUC 48 h (119 +/- 22 vs. 133 +/- 13 mg/h/L), or AUCO--infinity ( 221 +/- 40 vs. 203 +/- 41 mg/h/L) were noted. Absorption was variable for both preparations. The relative bioavailability using the tablet as the standard formulation was (0.92 +/- 0.22). Transient, mild side effects were noted in three subjects with the chewable tablet alone, and one subject experienced side effects with both formulations. It was concluded that CBZ tablets and chewable tablets may be used interchangeably; however, considerable intra- and intersubject variability exists, and the need for patient monitoring is emphasized.

Adult↗
PubMed1987

Carbamazepine side effects in children and adults.

Most of the side effects associated with carbamazepine (Tegretol, USP, Geigy Pharmaceuticals) therapy are mild, transient, and reversible with an adjustment in dosage or rate of dosage increase. Direct reports to Geigy Pharmaceuticals for the period 1975 to 1986 totaled 371 hematologic, 396 dermatologic, and 156 hepatic and pancreatic occurrences out of more than 4 million patients treated. These include 27 cases of aplastic anemia and 10 of agranulocytosis. In a study of the incidence of side effects in 220 children below the age of 16 years who were receiving carbamazepine, drowsiness, loss of coordination, and vertigo were the most commonly observed side effects and were almost always transient and dose related. The findings of this study are comparable with those of other series assessing carbamazepine-associated adverse reactions in children and adults. Overall, 30 to 50% of children and adults were reportedly free of side effects in these studies. Recommendations for carbamazepine therapy include education of patients and parents in the nature and likelihood of possible serious adverse reactions and routine monitoring to detect laboratory abnormalities.

Adult↗
PubMed1986

Influence of tube type, storage time, and temperature on the total and free concentration of valproic acid.

The influence of storage conditions on the total and free concentration of valproic acid (VPA) was studied in six normal male subjects who ingested 750 mg of VPA (3 X 250 mg Depakene capsules; Abbott Laboratories). Blood samples were collected in various types of Vacutainer tubes (red top, no additives; green top, sodium heparin; blue top, sodium citrate; and purple top, EDTA) 2 h post administration of VPA. Either these samples were centrifuged immediately or stored for various periods of time at room temperature or refrigerated, or the supernate was frozen prior to analysis. Free VPA samples were obtained utilizing the Amicon ultrafiltration system. All VPA samples were analyzed by gas-liquid chromatography. Total VPA concentrations obtained from plasma collected with sodium citrate were lower (p less than 0.05) than either serum or plasma collected with other anticoagulants. There were no differences (p greater than 0.05) in total or free VPA concentrations between samples collected in serum or in plasma collected with heparin or EDTA. Storing samples for 96 h at room temperature did not alter the total VPA concentrations but was found to increase the free fraction of VPA (p less than 0.05). The refrigeration or freezing of the supernate from the blood samples for 7 days did not alter (p greater than 0.05) the total or the free fraction of VPA. The results of this study demonstrate that total and/or free VPA may be collected from either serum or plasma, provided sodium citrate is not used to collect plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Specimen Collection↗