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Biomedical subjects

J J Cereghino

Publications and source records attributed to J J Cereghino.

At least 19 recordsLinked to original sources
PubMed2000

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. METHODS: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. RESULTS: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p </= 0.001 for both groups). More patients responded (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam than placebo, with rates of 33. 0% in the 1000 mg/day and 39.8% in the 3000 mg/day group, compared to 10.8% in the placebo group (p < 0.001). Of 199 patients receiving levetiracetam, 11 became seizure free; no patient became seizure free in the placebo group. Treatment-emergent adverse events (>/=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Adolescent↗
PubMed2000

Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group.

PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas. CONCLUSIONS: Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.

Adult↗
PubMed1999

Rectal diazepam gel for treatment of acute repetitive seizures. The North American Diastat Study Group.

The purpose of these investigations was to determine from combined data the response to rectal diazepam (DZP) gel (Diastat [Athena Neurosciences, South San Francisco, CA]) in home treatment of children with episodes of acute repetitive seizures (ARS). A subset of patients aged 2-17 years were selected from two prospective placebo-controlled studies of children and adults. In both studies a prospective, double-blind, placebo-controlled design was used. The treatment groups (68 DZP; 65 placebo) did not differ significantly in age, race, seizure type or etiology, or in the median number of ARS episodes per month before study entry. DZP-treated children demonstrated a significant reduction in median seizure frequency compared with the placebo group (0.00 vs 0.25 seizures per hour, P = 0.001). Significantly more DZP-treated children remained seizure free during the observation period (40 vs 20, P = 0.001). Somnolence was the only adverse effect present significantly more often in the DZP-treated children (25.0% vs 7.7%, P = 0.0095). There were no instances of serious respiratory depression. Rectal DZP was demonstrated to be an effective and safe treatment to abort an episode of ARS in a child and, additionally, lessened the likelihood of seizure recurrence within the next 12 hours.

Acute Disease↗
PubMed1999

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group.

PURPOSE: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of > or =5 days. METHODS: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single-use, prefilled syringe; dosage was determined by age and weight. Maximal use was > or =5-day intervals, < or =5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly. RESULTS: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty-five received two or more treatments (two to 78; median, 8), 0.03-4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months. CONCLUSIONS: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication-related AEs were seen with repeated DZPRG administration at intervals > or =5 days.

Administration, Rectal↗
PubMed1998

Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group.

OBJECTIVE: To evaluate the effectiveness and safety of a single-dose treatment for acute repetitive seizure (ARS) episodes (e.g., clusters) administered in a nonmedical setting by caregivers. BACKGROUND: Patients with epilepsy may experience ARS episodes despite optimal anticonvulsant treatment. Such episodes require rapid treatment as medical emergencies. Typically, the patient is treated in an emergency medical setting with i.v. medication by trained medical personnel. METHODS: The authors undertook a multicenter, randomized, parallel, double-blind study of a single administration of Diastat (diazepam rectal gel) for treating episodes of ARS. ARS episodes and treatment criteria were defined for each patient at the start of the study. Caregivers were taught to determine ARS episode onset, administer a predetermined dose of study medication, monitor outcome, count respirations, and record seizures and adverse events. RESULTS: A total of 29 centers enrolled 158 patients, of whom 114 patients had a treated ARS episode (Diastat, n = 56; placebo, n = 58). Diastat treatment reduced median seizure frequency (p = 0.029). More Diastat patients were seizure free post-treatment (Diastat, 55%; placebo, 34%; p = 0.031). Kaplan-Meier analysis of the time to the next seizure favored Diastat treatment (p < 0.007). The most common adverse event was somnolence. CONCLUSION: Administration of a single rectal dose of Diastat was significantly more effective than placebo in reducing the number of seizures following an episode of ARS. Caregivers could administer treatment safely and effectively in a nonmedical setting.

Acute Disease↗
PubMed1998

Six-month evaluation of Carbatrol (extended-release carbamazepine) in complex partial seizures.

We evaluated the use of a new, controlled-release capsule form of carbamazepine, Carbatrol capsules, in an open-label, multicenter study of 124 patients with complex partial seizures. Ninety-one percent of the patients successfully completed the 6-month trial with good seizure control, with a significant improvement in quality of life. We conclude that switching patients with complex partial seizures from multiple daily-dose carbamazepine to twice-daily Carbatrol on a milligram-to-milligram basis is relatively safe.

Adolescent↗
PubMed1994

Dezinamide for partial seizures: results of an n-of-1 design trial.

BACKGROUND: Dezinamide (DZM, ADD 94057) is a potential antiepileptic drug that binds to the voltage-sensitive sodium channel and showed preliminary evidence of efficacy and safety in an open-label study. METHODS: Our double-blind, placebo-controlled trial at two sites used an n-of-1 (single-patient) design. All 15 patients had medically intractable partial-onset seizures and were comedicated with phenytoin (PHT) only. Treatment was for six 5-week periods (three active paired with three placebo in random sequence). Assuming nonlinear kinetics, we used an initial pharmacokinetic profile to estimate dosages for reaching target plasma concentrations of DZM. RESULTS: Statistically significant seizure reduction was found by both a randomization test (p = 0.0025) and a signed rank test (p = 0.048). Median seizure frequency decreased 37.9%, and 40% of patients had > 50% seizure reduction, both compared with placebo. Pharmacokinetic predictions were not accurate; mean plasma concentrations fell well below target values. Plasma PHT concentrations increased (mean = 17.1%) during DZM treatment. The most common adverse experiences were fatigue, light-headedness, and abnormal gait; five patients required DZM dosage reductions. CONCLUSIONS: DZM showed minimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establishes the suitability of the n-of-1 design to investigational antiepileptic drug trials.

Adult↗
PubMed1991

Felbamate for partial seizures: results of a controlled clinical trial.

Felbamate (2-phenyl-1,3-propanediol dicarbamate) has a favorable preclinical profile in animal models of epilepsy. We present the results of a double-blind, randomized, placebo-controlled clinical trial in patients with partial seizures. Criteria for entry included a requirement for four or more partial seizures per month despite concomitant therapeutic blood levels of phenytoin and carbamazepine. Fifty-six patients (mean age, 31.4 years; 32 men, 24 women) completed the trial. The mean seizure frequencies for the 8-week periods analyzed were felbamate = 34.9, placebo = 40.2. Felbamate was statistically superior to placebo in seizure reduction, percent seizure reduction, and truncated percent seizure reduction. The mean felbamate dosage was 2,300 mg/d. Plasma felbamate concentrations ranged from 18.4 to 51.9 mg/l, mean = 32.5 mg/l. Adverse experiences during felbamate therapy were minor and consisted primarily of nausea and CNS effects. This trial indicates that felbamate is safe and effective in the treatment of comedicated patients with severely refractory epilepsy.

Adult↗
PubMed1985

Advances in the clinical development of antiepileptic drugs.

In this paper we describe advances in the clinical development of antiepileptic drugs as a function of the Antiepileptic Drug Development Program of the National Institute of Neurological and Communicative Disorders and Stroke. This program encompasses both the preclinical and clinical elements of drug development through the Anticonvulsant Screening Project, the Toxicology Project, and the support of controlled clinical trials of potential new drugs that emerge from these projects and promise to be more effective and less toxic than those currently available for the treatment of epilepsy.

Animals↗
PubMed1975

The dermatoglyphics of American Negroes.

Digital and palmar dermatoglyphics of 184 male and 224 female normal American Negroes were evaluated for digital patterns, digital ridge counts, palmar patterns, palmar main line terminations, accessory triradii and palmar creases. All subjects were seven year olds examined and found free of chronic or other genetic diseases. The results were presented for the left and right hand separately as well as in terms of bilateral symmetry. The present results were for the most part comparable to those of the African and other American Negro groups reported earlier. The distributions of the various dermatoglyphic features among the Negroes taken as a group were compared to those of the other racial groups and their differences were discussed.

Africa↗
PubMed1975

The dermatoglyphics of American Caucasians.

Digital and palmar dermatoglyphics were collected from 360 male and 360 female seven year old Caucasians from the greater Boston area. All participants were screened and found to be free of minor anomalies or chronic diseases. All individuals with I. Q. scores below 70 were also excluded. The results were presented in such a way as to give information on bilateral symmetry as well as overall frequencies of the various dermatoglyphic features. The results were compared with those of the corresponding sample of seven year old normal male and female Negroes of the accompanying report. A review of the distribution of the dermatoglyphic features in different Caucasian populations has also been presented and the overall dermatoglyphics of the Caucasians were discussed in reference to the distribution of the same features in the other major "racial" groups. The method of collection and selection of the subjects, described in the text, makes this set of data unique and one of the most suitable for use as controls in studying the dermatoglyphics of the individuals with diseases or congenital anomalies.

Black or African American↗
PubMed1975

The efficacy of carbamazepine combinations in epilepsy.

The efficacy and bioavailability, and tolerance to carbamazepinee when administered with phenobarbital or phenytoin or with both drugs were evaluated in a prospective, double-blind study of patients whose seizures were not completely controlled by currently available antiepileptic drugs in usually therapeutic dosages as determined by serum levels. During each of four 21-day treatment periods, one fourth of the patients received daily doses of: (1) carbamazepine (1,200 mg) and phenytoin (300 mg); (2) carbamazepine (1,200 mg) and phenobarbital (300 mg); (3) phenytoin (300 mg) and phenobarbital (300 mg); or (4) carbamazepine (1,200 mg), with phenytoin (300 mg) and phenobarbital (300 mg). The treatment periods were separated by 2 wk of each patient's usual prestudy medication. Treatment with all three drugs was the most efficacious for seizure control. Serum carbamazepine concentration was significantly decreased when the drug was administered with either phenytoin or phenobarbital or both.

Adult↗
PubMed1975

A single-dose study of mexiletine (Kö 1173).

Serum concentrations of mexiletine after a single dose were determined in 8 adult Caucasian males with complex partial seizures who were continuing to receive other antiepileptic drugs. Two patients each received a single dose of either 100, 200, 300, or 400 mg mexiletine. Serum concentrations were determined by two gas chromatographic methods. Serum concentrations ranged up to 795 ng/ml. Peak concentrations occurred 1 to 3 hr after administration of the drug and were significantly different between the 100- and 300-mg, 100- and 400-mg, 200- and 300-mg, and 200- and 400-mg doses. Differences between the other doses were not significant. Serum concentrations declined monoexponentially. Half-life ranged from 2.7 to 7.2 hr. Numerous papers have appeared in the European literature on the use of mexiletine to treat cardiac arrhythmias. Preliminary studies in the United States suggest the use of mexiletine as an adjunct for therapy of epilepsy.

Adult↗
PubMed1975

A multiple-dose study of mexiletine (Kö 1173).

In preparation for a prospective controlled study of mexiletine in the treatment of epilepsy, a preliminary study of serum concentrations after multiple doses was performed with 8 institutionalized Caucasian adult males with uncontrolled seizures and similar weight, medical regimen, and seizure classification. Two patients each received daily dosages of 200, 400, 600 or 800 mg mexiletine administered in capsules four times a day for 7 days, in addition to their usual medication. Serum concentrations of mexiletine were determined by the Kupferberg-Yonekawa method. After the first day, serum concentrations of mexiletine were significantly higher for the 600 and 800-mg dosages than for the 200- and 400-mg dosages. The differences in serum concentration between the 200- and 400-mg dosages and between the 600- and 800-mg dosages were not significant. Serum concentrations for the 200-mg and 400-mg dosages were generally below 400 ng/ml, whereas at dosages of 600- and 800-mg, serum concentrations ranged from 400 to over 1,100 ng/ml, after the first day. Optimal dosage for this population appeared to be at least 800 mg/day. Half-life ranged from 3.5 to 7.8 hr.

Adult↗