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Biomedical subjects

L Gram

Publications and source records attributed to L Gram.

At least 109 records · Page 6Linked to original sources
PubMed1985

gamma-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy.

The antiepileptic effect of gamma-vinyl gamma-aminobutyric acid (GABA), an irreversible GABA-transaminase inhibitor, was investigated in an add-on, placebo-controlled, double-blind, cross-over, fixed-dose trial. Twenty-one patients suffering from difficult to control complex partial seizures participated; 18 patients completed the trial. Serum levels of concomitant antiepileptic drugs were kept constant throughout the trial. Three patients (17%) experienced a 75% reduction in seizure frequency and in 8 (44%) the seizures were reduced by at least 50%. Two patients developed a moderate and 1 patient a marked increase in seizure frequency during treatment with gamma-vinyl GABA. Except for 2 patients who had to discontinue the trial because of adverse effects of gamma-vinyl GABA, the participants were unable to discriminate between treatment regimens with regard to side effects. gamma-vinyl GABA seems to be a promising new antiepileptic drug, and the first one to present convincing evidence of a GABAergic mechanism of action.

Adolescent↗
PubMed1985

Valproate: an updated review.

Valproate in all its aspects is comprehensively surveyed. Previous reviews covering various aspects such as mechanism of action, clinical pharmacology, clinical efficacy in epilepsy, febrile convulsions and other neurological disorders, side effects, teratogenicity and intoxications are discussed and updated (161 references).

Abnormalities, Drug-Induced↗
PubMed1985

Long-term study of gamma-vinyl GABA in the treatment of epilepsy.

The purpose of this study was to investigate the long-term efficacy and tolerability of gamma-vinyl GABA (GVG) in the treatment of epilepsy. 36 patients with severe therapy resistant epilepsies participated, the majority exhibiting complex partial seizures. The mean follow-up period was 9.3 months. GVG was administered as add-on therapy, to keep serum levels of concomitant treatment constant. The mean dose of GVG was 2.6 g's per day. Fifty-six per cent of the patients, including three patients with juvenile myoclonic epilepsy, experienced more than a 50% reduction in seizure frequency. No signs of tolerance development to the antiepileptic effect of GVG was demonstrated. Two patients were withdrawn from GVG treatment due to increased seizure frequency, and two due to side effects in the form of vomiting and nausea. Incidentally, the side effects observed were harmless and transient. Fifty per cent of the patients experienced no side effects at all. GVG seems to be a valuable antiepileptic compound. The results of this long-term study confirm observations from several short controlled trials.

Adolescent↗
PubMed1984

Weight gain during treatment with valproate.

An analysis was made of weight changes during treatment with valproate in 63 adult epileptic patients. 36 patients (57%) gained more than 4 kg in weight during treatment, while 27 patients (43%) were stable in weight with weight changes of less than +/- 4 kg. There were no significant differences between weight gainers and weight-stable patients with regard to age, sex, pretreatment overweight, duration of treatment, dosage or serum levels of valproate. From structured patient interviews, it appeared that the 2 groups of patients differed only insignificantly with regard to appetite, thirst and familial predispositions to obesity and diabetes. Consequently, no factors predictive for weight gain could be outlined. Presumable pathogenic mechanisms of importance are discussed.

Adult↗
PubMed1984

The effects of carbamazepine and valproate on folate metabolism in man.

The effect of carbamazepine and valproate treatment on folate metabolism was studied in 11 epileptic patients. The absorption of folic acid and of Pteroyl-gamma-L-glutamyl-gamma-L-glutamyl-L-glutamic acid, a synthetic substrate for intestinal folate deconjugase , was measured prior to and after 2 months of antiepileptic therapy with either carbamazepine (5 cases) or valproate (6 cases). After 2 months' treatment, the area under plasma concentration versus time curve was significantly decreased and t-max (time when maximal plasma concentration is obtained) was significantly prolonged. No inhibition of intestinal folate deconjugation was observed and the liver metabolism of folic acid was found to be unaffected by the treatment. These findings are interpreted as an inhibition of intestinal folic acid absorption caused by the antiepileptic therapy.

Adolescent↗
PubMed1983

Intellectual and social function of patients surviving cardiac arrest outside the hospital.

Thirteen survivors of cardiac arrest outside the hospital were examined by clinical and psychological tests 1-3 years after the incidence, and compared to a matched control group of 13 patients with acute myocardial infarction without cardiac arrest. Psychological tests revealed that 7 patients with previous cardiac arrest and 4 control patients had mild-moderate to moderate-severe dementia. The demential symptoms were not detectable by a clinical interview. Four patients in each group exhibited pronounced anxiety symptoms. There were no clear differences between the two groups in respect of changes in cardiac function and social status after the incidence.

Adult↗
PubMed1983

Progabide: a controlled trial in partial epilepsy.

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.

Anticonvulsants↗
PubMed1983

Hepatic toxicity of antiepileptic drugs: a review.

Hepatic toxicity of antiepileptic drugs has been well recognized for many years. Despite the increasing awareness of chronic toxicity of antiepileptic drugs, this aspect has remained of limited importance. Since the introduction of valproate, this situation has changed fundamentally. Following a general introduction to the classification and symptomatology of drug-induced hepatic toxicity, a detailed description of hepatic toxicity caused by phenytoin, carbamazepine, and valproate is presented, including classification, symptomatology and histological features. Hepatic toxicity caused by all three drugs may be classified as idiosyncratic reactions. However, whereas toxic reactions following phenytoin and carbamazepine are characterised by a rather short duration of exposure before symptoms occur with accompanying clinical features of hypersensitivity, valproate-induced hepatic toxicity exhibits no signs of hypersensitivity and often occurs following prolonged exposure, speaking in favor of a metabolic aberration as the underlying cause. Hypotheses explaining the mechanisms involved in this phenomenon are reviewed. Guidelines for averting valproate-induced hepatic toxicity are presented.

Anticonvulsants↗
PubMed1983

Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. A controlled study.

Studies investigating the influence of antiepileptic drugs on thyroid hormones usually have compared patients chronically treated with antiepileptic drugs to controls. To date, this type of designs has produced divergent results both with regard to individual drugs and individual thyroid hormones. The present study comprised 31 patients with newly diagnosed epilepsy, commencing treatment with either carbamazepine or valproate. T3, T4, FT4, FT3, rT3, TSH, T3 resin uptake and blood folic acid, were determined before and during antiepileptic monotherapy, thus making the patient his own control. During treatment with carbamazepine, a significant decrease in T4, FT4, FT3, rT3 and TBG was observed. Valproate caused a decrease in T4, FT4 and T3. Neither of the drugs caused any changes in blood folic acid concentrations or persistent increases in the TSH values. None of the patients developed overt symptoms of hypothyreoidism. Conceivable mechanisms underlying these hormonal changes are reviewed.

Adolescent↗
PubMed1983

Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy.

The anti-epileptic effect of gamma-vinyl-GABA (GVG) was studied using a placebo-controlled, single-blind design in 15 patients with therapy-resistant epilepsy, the majority experiencing complex partial seizures. GVG was added to concomitant treatment, which was kept at constant serum levels. Following administration of 1 g, 2 g and 3 g per day, significant reductions in seizure frequency were observed. A poor correlation was found between GVG serum levels and clinical effect. Only mild and transient side-effects were observed.

Adolescent↗
PubMed1982

Controlled trials in epilepsy: a review.

A comprehensive review, evaluating 51 randomized double-blind controlled studies, covering different aspects of epileptology, is presented. Trials were grouped according to the investigated topic and for each group an attempt was made to derive an overall conclusion. The majority of studies investigated antiepileptic drug treatments. Other topics were: psychotropic effect of antiepileptic drugs, folic acid and vitamin D administration in epilepsy, and EEG investigations. A cross-sectional analysis of items such as designs, patient sampling principles, recording of effect parameters and side effects, concomitant treatments, and statistical evaluations demonstrated that cross-over designs, investigating fixed dosage schedules, were extensively used. Less than half of these studies included a washout period between treatments, complicating the interpretation of the obtained results. The vast majority of studies involved only chronic patients; and marked heterogeneity in patient selection with respect to age, seizure type, and mental status, and severity of epilepsy was observed. Classifications of seizures varied between the studies. The most prominent effect parameter was seizure frequency. The use of heterogeneous patient samples frequently necessitated equalization of widely different seizure types in order to perform statistical analyses. The mean duration of trials was 6 months, precluding evaluation of chronic toxicity. The majority of studies recorded side effects, but data collection was rather unsystematic and statistical evaluation was seldom applied. Most studies were add-on trials, and since concomitant treatment was frequently changed during the investigations, it was difficult to evaluate the influence of this variable. A correlation analysis across trials demonstrated, among other things, that the common assumption that short controlled trials provide too optimistic results, could not be substantiated. This survey provides no firm indication of which drug is more suitable for which seizure type.

Anticonvulsants↗
PubMed1979

Sodium valproate, serum level and clinical effect in epilepsy: a controlled study.

Clinical effects at three different serum levels of sodium valproate (VPA) were compared in a triple-blind, multiple crossover trial comprising 13 epileptic inpatients. Patients were selected regardless of seizure type, and all were in concomitant antiepileptic treatment, which was kept constant throughout the study. A significant relationship between the decrease in number of seizures and increasing VPA serum level was demonstrated. The relationship between VPA dose and serum level was curvilinear. Statistical evaluation of patients by seizure type in relation to clinical effect of VPA was only possible for secondary generalized seizures. Between phenytoin, phenobarbital, and carbamazepine and the different VPA serum levels no interactions could be demonstrated. Recorded side effects were always mild and transient. No obvious correlation between side effects and VPA serum level was established.

Adolescent↗