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Biomedical subjects

F J Vajda

Publications and source records attributed to F J Vajda.

At least 19 recordsLinked to original sources
PubMed2001

Prospective study of local cutaneous reactions in patients receiving IV phenytoin.

The authors prospectively examined the occurrence of subacute local cutaneous reactions (LCR) in patients receiving IV phenytoin over a 12-month period at a general hospital. LCR were detected in 29 of 115 patients (25.2%; 22 mild and seven moderate). All resolved within 3 weeks. Patients with LCR were older (median 68 versus 54.5 years, p = 0.004), were more likely to be in a general ward (86% versus 66%, p = 0.04), and had larger catheters (median 16 G versus 18 G, p = 0.05). The authors conclude that LCR are common in routine hospital practice, but are generally mild and benign.

Adult↗
PubMed2001

Epilepsy, depression and antidepressant drugs.

Apart from constituting an important management problem, depression coexisting with epilepsy is also an interesting psychiatric phenomenon, with multiple interacting biological, psychological and social factors involved in its causation. New research approaches to the study of epilepsy and depression, including neuroimaging, neurochemical and neuroendocrine techniques, and the arrival of new classes of antidepressants in recent years, suggest it is timely to reconsider this topic. We review current knowledge of the prevalence and causes of interictal depression in epilepsy, focussing mainly on neurobiological factors, and give an overview of recent concepts concerning the management of depression. We also discuss pharmacological treatment of depression in epilepsy, focussing on the association between antidepressants and seizures, and drug interactions.

Antidepressive Agents↗
PubMed1999

Determination of lamotrigine in human plasma by high-performance liquid chromatography.

The method involves precipitation of plasma proteins with acetonitrile and analysis of the supernatant by high-performance liquid chromatography using a 5 microm Zorbax C8 column. Quantitation was performed by measurement of the UV absorbance at a wavelength of 306 nm. The method was linear in the range of 1-20 microg/ml, with a mean coefficient of determination (r2=0.998). The limit of detection was 0.6 microg/ml and the lower limit of quantitation was 1 microg/ml using 200 microl of plasma. Within- and between-day accuracy and precision were below 6% at all analysed concentrations except at the limit of quantitation. No interfering peaks were found by commonly monitored antiepileptic drugs. Recovery was found to be > or =99%. Satisfactory performance was obtained in the evaluation of epileptic patient samples, whose results of plasma concentration measurements are briefly discussed. We conclude that this is a reliable method for the routine monitoring of lamotrigine concentration in plasma in the clinical setting.

Adult↗
PubMed1998

Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy.

PURPOSE: Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatment-resistant generalised epilepsy. METHODS: The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG. RESULTS: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 350% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had > or =50% seizure reduction and five (25%) were seizure free. CONCLUSIONS: This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.

Adolescent↗
PubMed1993

Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures.

The results of a multicentre, randomised, double-blind, placebo controlled, crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs (AEDs) are presented. The study consisted of two 12 week treatment periods each followed by a four week washout period. During the lamotrigine treatment phase, patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1-3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study. There was a highly significant (p < 0.001) decrease in total seizure counts on lamotrigine compared with placebo. Overall, 22% of patients experienced at least a 50% reduction in the total numbers of all seizures types on lamotrigine, compared with none on placebo. When the total numbers of partial seizures (simple and complex partial) were analysed there was also a significant (p < 0.05) reduction in seizure counts on lamotrigine compared with placebo. When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance (0.05 < p < 0.1). Concomitant AED plasma concentrations were virtually unchanged. It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures.

Anticonvulsants↗
PubMed1992

New anticonvulsants.

The development of antiepileptic drugs has been rather slow, and this may be related partly to the regulatory requirement to show unequivocal benefit of a new agent over existing drugs. There is a need to reconsider trial protocols to achieve this objective. Five new drugs, vigabatrin (GVG), lamotrigine (LTG), gabapentin (GPT), felbamate and oxcarbazepine (OCBZ) appear to be the most widely tested and promising agents. Of the others, loreclezole and stiripentol (STP) are showing the highest potential for therapeutic application. Clobazam appears to be more effective than implied from earlier reports.

Animals↗
PubMed1989

Effects of the NMDA receptor antagonist MK-801 against amygdaloid-kindled seizures in the rat.

The effects of acute and subchronic administration of the noncompetitive NMDA receptor antagonist MK-801 on the duration and severity of amygdaloid-kindled seizures in rats were determined to evaluate its anticonvulsant activity. Both the highest acute (1000 micrograms/kg) and subchronic regimens (2 x 300 micrograms/kg, 7 days) produced significant reductions in the seizure stage and afterdischarge duration. Although ataxia may have affected the seizure stage, MK-801 attenuated the primary afterdischarge suggesting anticonvulsant effects in the fully amygdaloid-kindled rat. Since tolerance develops to the behavioral effects of MK-801, other noncompetitive NMDA antagonists related to MK-801 seem to warrant evaluation as anticonvulsants.

Amygdala↗
PubMed1988

Regional brain concentrations of cholecystokinin in the rat: the effects of kindled and non-kindled seizures.

In an attempt to understand the neurochemical basis of kindling, this study investigated the effects on brain cholecystokinin (CCK) of amygdaloid kindled and non-kindled seizures. Thirteen brain regions were examined in rats sacrificed either 24 hr or 3 weeks after the last kindled seizure, or 24 hr after a suprathreshold stimulation-induced (non-kindled) seizure; and in sham kindled rats. There were no significant differences in CCK immunoreactivity between any of these groups. These results do not confirm a previous report of an increase in CCK in the hippocampus following amygdaloid kindling in the rat.

Animals↗
PubMed1988

Relationship between the dose-response effects of diazepam and clobazam on electroencephalographic parameters and on kindled amygdaloid seizure activity in rats.

1. The possibility that the anticonvulsant activity of the benzodiazepines, diazepam and clobazam, is related to changes in EEG parameters, particularly beta activity, was investigated in amygdaloid kindled rats. 2. The effects of diazepam (1, 2, 4, 8 and 16 mumols/kg), administered intraperitoneally (i.p.), clobazam (1, 2, 4, 8, 16 and 32 mumols/kg, i.p.) or vehicle (dimethyl sulfoxide) on the cortical EEG of amygdaloid kindled rats were quantitated for 15 min using computerized period amplitude analysis. Immediately afterwards, the amygdala was stimulated and the after-discharge duration (AD) and the seizures stage (SS) were determined. 3. The equivalent percentage time (EPT) of the diazepam-treated group was decreased in the theta band (4-8 Hz) and increased in the alpha (8-12 Hz) and first six beta (12-36 Hz) bands. The mean peak amplitude (MPA) was increased in the alpha (8-12 Hz) and all seven beta bands (12-40 Hz). Clobazam increased the EPT and MPA in the alpha (8-12 Hz) and all seven beta (12-40 Hz) bands. The MPA was also increased by clobazam in the theta (4-8 Hz) band. 4. Diazepam reduced both the AD and SS of the kindled seizures at doses of 4, 8 and 16 mumols/kg, whereas clobazam was anticonvulsant at doses of 16 and 32 mumols/kg. The reduction in both AD and SS correlated with increases in the EPT and MPA in the first beta (12-16 Hz) band in the diazepam-treated group and in the first four beta (12-28 Hz) bands in the clobazam-treated group.

Amygdala↗
PubMed1988

Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat.

The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg-1), clonazepam (0.3 mg kg-1) or vehicle (1 mL kg-1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor.

Amygdala↗
PubMed1987

The current status of monoamine oxidase and its inhibitors.

The enzyme monoamine oxidase (MAO) plays an important role in the inactivation of both dietary amines and also of neurotransmitter amines. A study of the properties of irreversible inhibitors of this enzyme suggests that the enzyme exists in two broad types--MAO-A and MAO-B. Although irreversible inhibitors of MAO were once widely used as antidepressant agents, they fell from favour because of adverse reactions after the ingestion of amine-containing foodstuffs ("the cheese reaction"). However, these inhibitors (phenelzine and tranylcypromine) are probably best for the treatment of atypical depression providing the patient is aware of dietary reactions. A new series of reversible, MAO-A selective inhibitors are being developed which do not exhibit serious dietary interactions. These reversible inhibitors show promise as rapidly acting antidepressant agents. An atypical irreversible MAO-B selective inhibitor, selegiline (deprenyl) does not exhibit an adverse reaction on the ingestion of amine-containing foods. This drug has been used as an adjuvant in the treatment of Parkinson's disease since it allows the dose of L-dopa to be reduced by approximately 25%. More important, selegiline may slow the degeneration of dopaminergic neurons that is characteristic of Parkinson's disease.

Allylamine↗
PubMed1987

Microcomputer analysis techniques for evaluation of benzodiazepine effects on rat electrocorticogram.

Quantitative analysis of drug effects on the EEG is usually performed on a minicomputer using an EEG signal that has been recorded on a high frequency FM tape recorder and edited to remove artefact. However, this equipment is expensive and so the present study evaluated a much cheaper system, an 'on-line' microcomputer and 3 programs for data reduction. Using this system to assess diazepam effects on the rat electrocorticogram, it was concluded that period amplitude analysis may be preferable to the Fast Fourier Transform or Hjorth analysis.

Animals↗
PubMed1987

The development of tolerance to the anticonvulsant effects of clonazepam, but not sodium valproate, in the amygdaloid kindled rat.

The effects of chronic treatment with clonazepam and sodium valproate were studied on kindled amygdaloid seizures in rats. Fully kindled rats were given an intraperitoneal (i.p.) injection of either vehicle (1.0 ml/kg), clonazepam (0.3 mg/kg) or sodium valproate (200 mg/kg) twice daily for 12 days. Each rat was stimulated through an amygdaloid electrode 30 min after the morning dose. While both drugs initially blocked and kindled seizure (P less than 0.01), the results showed a significant trend (P less than 0.02) in the development of tolerance to the anticonvulsant action of clonazepam but no significant tolerance to the action of valproate.

Amygdala↗
PubMed1987

Tolerance to the anticonvulsant effects of clonazepam and clobazam in the amygdaloid kindled rat.

A major problem in the treatment of clinical epilepsy with benzodiazepines is the development of tolerance. This is most marked with the 1,5-benzodiazepine, clobazam, but is also noted with the 1,4-benzodiazepine, clonazepam. This study examined the effects of chronic treatment with clobazam, clonazepam and the non-benzodiazepine sodium valproate on the amygdaloid kindled rat with a view to developing an animal model of tolerance. Twice daily intraperitoneal injections of vehicle (1 mL/kg), clonazepam (0.3 mg/kg), clobazam (4.0-8.0 mg/kg) or sodium valproate (200 mg/kg) were given to fully kindled rats for 12 days, in the case of clonazepam and valproate, and for 16 days for clobazam. All rats were stimulated 30-60 minutes (depending on the drug) after the morning dose. The amygdala after-discharge duration (recorded on the EEG) and the seizure stage were determined. While all three drugs initially blocked the kindled seizure, tolerance developed to clonazepam and clobazam but not to valproate. Statistical analysis of the results showed a significant linear trend in the development of tolerance to clonazepam after day 5, but tolerance to clobazam appeared in a more abrupt manner after day 2. The clobazam group were then given a further 2 days of treatment with clonazepam (0.3-0.6 mg/kg) and this blocked the kindled seizures. The amygdaloid kindled rat is a suitable model for studying tolerance to the anticonvulsant effects of benzodiazepines. Further experiments are currently in progress to examine the effectiveness of change-over therapy between clobazam and clonazepam as a means of overcoming tolerance.

Amygdala↗
PubMed1986

The neurochemical and clinical effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in small animals.

The recent discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a syndrome of Parkinsonism in man and monkey has stimulated the search for a small animal model of Parkinsonism. In this study, MPTP was administered to a series of small animals and observations made on clinical and neurochemical changes. The clinical effects of MPTP in rabbits, guinea pigs, and rats were short lived, and no chronic Parkinsonian syndrome developed. The C57 black mouse, however, although also not showing clinical changes, proved to be an ideal neurochemical model in which to study the effects of MPTP since striatal dopamine levels were reliably reduced to 13% of control values after 4 intraperitoneal injections of 30 mg/kg MPTP. Pathological study of the striatum and substantia nigra in the mouse model failed to show any alteration in neuronal morphology or numbers. Although the effect of MPTP on striatal dopamine lasted for up to 2 weeks after the last MPTP injection, the possibility exists that no neurotoxic effects occur and the observed dopamine depletion is pharmacological only.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗