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Biomedical subjects

R A Gillham

Publications and source records attributed to R A Gillham.

12 recordsLinked to original sources
PubMed2002

A clinical neurological, neurophysiological, and neuropsychological study of sheep farmers and dippers exposed to organophosphate pesticides.

OBJECTIVES: To classify clinical diseases of the subjects with abnormal indices of peripheral neuropathy identified in field studies of sheep farmers and dippers exposed to organophosphate pesticides. To explore what neuropsychological profiles, if any, may be associated with neurophysiological damage in these subjects. METHODS: A case-control study (79 subjects) nested within the cross sectional study (685 subjects) of sheep farmers from the field study. Three groups with no, possible, and probable or definite neuropathy according to field studies were recruited. Investigations comprised symptoms of neuropathy, neurologial signs, motor and sensory nerve conduction, electromyography, quantitative sensory testing, and neuropsychological tests. RESULTS: The incidence of clinical neuropathy increased from 7% in the no neuropathy group to 52% in the probable or definite neuropathy group based on nerve conduction measurements or presence of neurological signs. Sensory abnormalities were found more often than motor deficits. Small diameter nerve fibres were also affected more than large fibres. CONCLUSIONS: The neuropathy is predominantly sensory and is characteristic of distal, chronic neuropathy with no acute features. Small fibre populations are affected more than large fibre populations. Increasing severity of neuropathy was associated with anxiety and depression as measured in the neuropsychological tests.

Adolescent↗
PubMed1994

A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P < 0.05). 5. No other differences in AUCs or elimination half-lives for OHCZ were found between treated and untreated patients following single or multiple OXC dosing. 6. Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo. 7. Ten patients completing the study complained of side-effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction.

Adult↗
PubMed1993

Double dummy comparison between once and twice daily dosing with modified-release carbamazepine in epileptic patients.

1. Fourteen patients with refractory epilepsy on a twice daily regimen of modified-release carbamazepine (CBZ-MR. Tegretol Retard. Ciba Pharmaceuticals) completed a balanced, double-blind, double dummy, random order, crossover comparison of 8 weeks treatment with once (o.d.) and twice daily (b.d.) dosing. In order to obtain a profile of serum CBZ concentrations over 24 h on once daily dosing, patients were randomised to taking it in the morning (o.d. a.m.) or evening (o.d. p.m.) for 4 weeks. Each treatment was taken with a placebo of the other and total tablet numbers were matched. Blood sampling was undertaken 0, 2, 4, 6, 8, 10, 12 and 24 h after the morning tablets at the end of each 4 week treatment period. 2. Overall, trough serum drug concentrations (Cmin) were lower with once daily dosing (Cmin: b.d. 7.5 mg l-1, o.d. 6.5 mg l-1, P < 0.05, 95% CI of the difference -1.3 to -0.1), but no significant differences were found in average (Cav) or peak (Cmax) concentrations, AUC values or fluctuations in CBZ concentrations. 3. Pharmacokinetic parameters for CBZ 10.11 epoxide, the active metabolite of CBZ did not differ significantly between the dosage schedules. 4. Seizure control was similar during once and twice daily dosing with CBZ-MR (median seizures/month (range): b.d. 1 (0-14.5), o.d. 0.5 (0-11), NS, 95% CI of the difference -1.8 to + 0.25). 5. There were no differences in psychomotor performance between the treatment periods. 6. More patients (n = 11) preferred treatment (P < 0.05) with once daily than twice daily dosing (n = 3) with CBZ-MR. 7. Once daily dosing with CBZ-MR should be possible in the majority of patients receiving the drug as monotherapy.

Adult↗
PubMed1993

Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy.

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation.

Adolescent↗
PubMed1992

Variability and clinical relevance of the interaction between sodium valproate and carbamazepine in epileptic patients.

Twenty-four epileptic patients (16 females, 8 males; aged 13-62 years) were studied before and after the addition of sodium valproate (VPA) 500 mg twice daily for 5 days. All had been established previously on carbamazepine (CBZ) as monotherapy (300-1600 mg daily in divided doses). Sixteen of these patients undertook a battery of cognitive function tests before and after VPA introduction. VPA had no effect on total or free CBZ concentrations. However, median concentrations of the active metabolite, CBZ 10,11 epoxide (CBZ-E), were significantly increased (CBZ-E before VPA 1.3 mg/l, after VPA 2.1 mg/l, P less than 0.01). The median rise was 25%, although the extent of the interaction ranged from a 25% decrease to an increase of 123% in CBZ-E concentrations. This was related to the marked inter-individual variation in circulating VPA (mean 25-69 mg/l), as CBZ-E concentrations correlated significantly with total (r = 0.5, P less than 0.05, 95% CI 0 to +0.08) and free (r = 0.7, P less than 0.001, 95% CI +0.09 to +0.25) VPA levels in individual patients. Although uncontrolled, no deterioration in performance of any of the cognitive function tests was observed following the addition of VPA. This study does not support immediate clinical relevance for this drug interaction between VPA and CBZ.

Adolescent↗
PubMed1991

Monotherapy with conventional and controlled-release carbamazepine: a double-blind, double-dummy comparison in epileptic patients.

1. Twenty-one epileptic patients completed a double-blind, double-dummy, random order, crossover comparison of conventional carbamazepine (CBZ, Tegretol, Ciba-Geigy) with a new controlled-release formulation (CBZ-CR, Tegretol Retard). All participants were stabilised on maximally tolerated doses of CBZ as monotherapy (one twice daily, twelve three times daily, eight four times daily). Each preparation was taken with a matched placebo of the other for 4 weeks. 2. Peak serum CBZ concentrations (mean +/- s.e. mean) were lower (CBZ 11.4 +/- 0.4 mg l-1; CBZ-CR 10.4 +/- 0.5 mg l-1; P less than 0.01) and times to peak longer (CBZ 3.6 +/- 0.5 h, CBZ-CR 5.2 +/- 0.7 h, P less than 0.01) during CBZ-CR treatment. Mean CBZ concentrations, however, were also slightly reduced with the new formulation (CBZ 9.9 +/- 0.3 mg l-1; CBZ-CR 9.1 +/- 0.5 mg l-1, P less than 0.05) and this was associated with greater seizure frequency (CBZ 2.8 +/- 1.2, CBZ-CR 3.8 +/- 0.9; P less than 0.05) during the CBZ-CR treatment phase. 3. Diurnal fluctuations (CBZ 41 +/- 3%, CBZ-CR 28 +/- 2%, P less than 0.01) and variations (CBZ 53 +/- 5%, CBZ-CR 33 +/- 3%; P less than 0.01) in serum CBZ concentration were substantially less with CBZ-CR and were similar to those calculated during a 6 or 8 hourly dosage interval with conventional CBZ (fluctuation 33 +/- 3%, variation 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cognitive function in adult epileptic patients established on anticonvulsant monotherapy.

A battery of psychometric tests was administered to 110 patients with epilepsy and to 24 non-epileptic controls. Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months. The remaining 26 patients were untreated at the time of study. No individual test discriminated between the groups. Tests were converted to standard scores and summated to give overall psychomotor, memory and side-effect assessments. There were no important differences between the performances of untreated epileptic patients and non-epileptic controls. The CBZ-treated patients had poorer psychomotor scores than both control groups and the VPA-treated patients (all P less than 0.05). The PHT patients scored less well on the composite memory scale than did VPA patients and non-epileptic controls (both P less than 0.05). There were no significant differences in subjective side-effects among the groups. This study demonstrated that anticonvulsant monotherapy has little effect on overall cognitive function in patients tolerating treatment. Psychomotor performance appeared to be selectively influenced by CBZ and memory impaired by PHT. VPA may be the drug to chose when cognitive function is an important consideration. Different cognitive modalities can be affected by different first-line anticonvulsants and this should be taken into account when choosing the most appropriate drug for an individual patient.

Adolescent↗
PubMed1988

Concentration-effect relationships with carbamazepine and its epoxide on psychomotor and cognitive function in epileptic patients.

A battery of psychometric tests was administered to 85 patients with epilepsy, of whom 26 were untreated, 40 received carbamazepine monotherapy and 19 took carbamazepine with another anticonvulsant. Carbamazepine alone had little effect on performance, but carbamazepine polypharmacy produced significant impairment. Increasing concentrations of carbamazepine (four tests) and its active metabolite, carbamazepine 10,11 epoxide (seven tests), correlated with decreasing performance in the monotherapy patients.

Adult↗
PubMedDate not supplied

Refractory epilepsy: an evaluation of psychological methods in outpatient management.

Two groups of adult outpatients (n = 19 and n = 21) with poorly controlled epilepsy and significant psychological disorder, assessed in terms of rating scales, received two psychological treatments in a balanced cross-over design after stable baseline seizure frequency had been established. A third group (n = 19), who had poorly controlled epilepsy but no significant psychological disturbance received one type of psychological treatment after a stable baseline. The treatments were educational and were designed to improve coping skills. Weekly seizure frequency was monitored for 42 weeks, and self-rating measures of anxiety and depression were obtained before treatment and at the end of follow-up. All three groups showed a significant reduction in seizure frequency that was maintained at 6-month follow-up. The two groups with psychological symptoms showed a significant improvement in scores on the self-rating scales. We concluded that routine use of psychological intervention may be helpful in outpatient management of epilepsy.

Adolescent↗
PubMedDate not supplied

Adjuvant vigabatrin in refractory epilepsy: a ceiling to effective dosage in individual patients?

A double-blind, randomized, cross-over study of additional vigabatrin (gamma-vinyl-GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) -1.5 to -14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI -18 to +24). Subgroup analysis, however, showed a significant reduction in partial seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI -0.5 to -16.5), but not with higher dosage (placebo 28, VGB 22, NS, 95% CI -18 to +11). A deterioration in control of partial seizures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to +20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic-clonic seizures. Serum VGB concentrations were higher during treatment with 3 g (15.5 +/- 8.9 mg/L) daily than with 2 g (13.5 +/- 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient.

Adolescent↗