A prospective controlled investigation of the cognitive effects of amateur boxing.

Eighty six amateur boxers underwent a series of neuropsychological assessments on three occasions--pre bout, immediate post bout and follow up within two years; 31 water polo players and 47 rugby union players acted as controls. The neuropsychological tests were selected as being sensitive to subtle cognitive dysfunction and formed part of a battery of other neurological and ophthalmic assessments. No evidence of neuropsychological dysfunction due to boxing was found, either following a bout or a series of bouts at follow up. None of a range of parameters including number of previous contests, recovery from an earlier bout, number of head blows received during a bout and number of bouts between initial assessment and follow up, were found to be related to changes in cognitive functioning.

Computed tomography findings in partial seizures.

The computed tomography findings in 82 children with partial seizures of unknown aetiology were reviewed. All had seizures with predominantly focal motor phenomena and none had abnormality on neurological examination. Findings on computed tomography were normal in 64 children (78%) and abnormal in 18 children (22%). Fourteen children had changes representing static pathology (mainly cerebral atrophy) which did not influence patient management but four had potentially correctable lesions (two tumours and two arteriovenous malformations). There were no correlations between seizure control, seizure duration, intellectual handicap, postictal weakness, electroencephalographic findings, and abnormality on the computed tomogram. In particular, none of these features were useful in predicting the presence of a tumour or arteriovenous malformation. It is concluded that a computed tomogram is indicated in every child with partial seizures.

Solid phase extraction of oxcarbazepine and its metabolites from plasma for analysis by high performance liquid chromatography.

A rapid, sensitive and simple-to-operate high performance liquid chromatographic method for the simulataneous determination of oxcarbazepine, 10-hydroxycarbazepine and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine in plasma is described. The drug and its metabolites were extracted from plasma using commercially available reversed phase octadecylsilane bonded-silica columns (Bond Elut C18, 1 mL capacity). Chromatographic separation of oxcarbazepine and its metabolites was achieved using a mobile phase consisting of acetonitrile/methanol/water (13:25:62 by volume) at a flow rate of 1.2 mL/min in conjunction with a Waters Associates Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a LiChrospher 5 microns C18 guard column. By measuring the UV absorbance at 214 nm, plasma levels in the region of 50-100 ng/mL for the drug and its metabolites can be detected with only 100 microL of plasma. The method has been applied to pharmacokinetic studies of oxcarbazepine and its metabolites in children with epilepsy; preliminary pharmacokinetic findings in two patients at steady-state are presented.

Daily variations in steady-state plasma concentrations of carbamazepine and its metabolites in epileptic children.

Total plasma carbamazepine, carbamazepine-10,11-epoxide (CBZ-EP) and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (CBZ-DIOL) concentrations were measured during a 24h period in 21 patients receiving carbamazepine monotherapy, in equally divided doses, every 12h. Interdose and diurnal variations in plasma concentrations of parent drug and metabolites were assessed. Carbamazepine and both metabolites showed significant differences in mean 4h post-dose plasma concentrations between day and night dosing (p less than 0.001). Significant linear correlations were obtained between carbamazepine dose and plasma concentrations of carbamazepine, CBZ-EP and CBZ-DIOL when sampling times were standardised (p less than 0.01). Comparisons of plasma concentrations of the parent compound with those of its 2 main metabolites revealed significant linear correlations in all cases (p less than 0.01). The effects of daily fluctuations in plasma concentrations of all 3 compounds on their relative concentrations (CBZ-EP:carbamazepine, CBZ-DIOL:carbamazepine and CBZ-DIOL:CBZ-EP) during the 24h period were also determined: the plasma concentration ratios CBZ-EP:carbamazepine and CBZ-DIOL:carbamazepine were significantly related to the dose of carbamazepine at fixed sampling times (p less than 0.05, with 1 exception). The large interdose and diurnal variation in plasma carbamazepine concentrations observed in this study (approximately 40% decrease from peak to trough) has important implications both clinically and in relation to therapeutic drug monitoring.

Dissolution and relative bioavailability of two carbamazepine preparations for children with epilepsy.

The in-vitro dissolution profiles of two carbamazepine formulations (Tegretol and a generic carbamazepine) have been assessed and the bioavailability of carbamazepine compared in 12 epileptic children at steady-state. Dissolution from the generic formulation (100 and 200 mg tablets) tended to be greater than for the proprietary tablets. However, the bioavailability and pharmacokinetics of carbamazepine when assessed at steady-state were similar for the two formulations. It appears, therefore, that the breakthrough seizures and higher incidence of neurological side-effects observed when children were given generic carbamazepine in place of the proprietary formulation cannot be accounted for by differences in bioavailability or pharmacokinetics.

Factors influencing plasma level/dose ratios of carbamazepine and its major metabolites in epileptic children.

The relationship between daily dose and plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-EP), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-DIOL) was investigated in 21 children aged 7-16 years who received CBZ monotherapy, twice daily in equally divided doses. Significant linear correlations between CBZ dose and plasma levels were obtained for CBZ and its metabolites (p less than 0.01). In addition, the effects of daily dose and patients' age on the plasma level/dose ratios for CBZ, CBZ-EP, and CBZ-DIOL were evaluated. A significant negative correlation was observed between the daily dose of CBZ and the CBZ plasma level/dose ratio (p less than 0.01). By contrast, plasma level/dose ratios for CBZ-EP and CBZ-DIOL were independent of dose (p greater than 0.1). On the basis of these observations, we consider that the decrease in CBZ plasma level/dose ratio with increasing CBZ dose appears to be due to dose-dependent metabolic clearance of CBZ. The influence of age on plasma level/dose ratios for CBZ and its metabolites was not significant (p greater than 0.05). However, there was considerable interdose and diurnal variation in the plasma level/dose ratios, particularly for CBZ (28-41%); this must be taken into account when making dose adjustments based on plasma level/dose ratios.

Breakthrough seizures with generic carbamazepine: a consequence of poorer bioavailability?

The bioavailability of carbamazepine from two products (Ethical Generics and Ciba-Geigy) and their efficacy with regard to seizure control and incidence of side-effects were compared in 23 children with tonic-clonic or complex partial seizures. Mean plasma concentrations of carbamazepine, carbamazepine 10, 11-epoxide and 10,11-dihydro-10, 11-trans-dihydroxy-carbamazepine at comparable sampling times were not significantly different during treatment with the two drug preparations. The incidence of seizures and occurrence of abnormal EEGs were not significantly different during treatment with the two carbamazepine preparations, and, in addition, the overall incidence of side-effects was not significantly different during the two treatment periods. However, neurological side-effects were significantly less during treatment with the Ciba-Geigy product. On the basis of these observations we are confident that the efficacy of these two carbamazepine preparations in children at steady-state is the same.

The body-worn alarm in the treatment of childhood enuresis.

Two studies examined the effectiveness of the body-worn alarm in out-patient treatment of childhood nocturnal enuresis. The first involved 40 children, previously untreated by conditioning methods, treated with either the body-worn alarm or the traditional pad and bell alarm. The second study compared the body-worn alarm with modified dry-bed training with 48 children previously resistant to treatment. Results of both studies indicated the body-worn alarm was as effective as other methods in terms of the proportion of children successfully treated and was superior with respect to rapidity of response and consumer appeal. Such findings indicate that the body-worn alarm could become the treatment of choice for nocturnal enuresis.

The child's construing of nocturnal enuresis: a method of inquiry and prediction of outcome.

Fifty-five children with nocturnal enuresis were engaged in a structured interview prior to treatment with the body-worn alarm. The interview sought to understand how children make sense of the experience and examines the implications for becoming dry. Successful treatment outcome was found to be associated with the child both construing bedwetting psychologically, and indicating no resistance to change. The importance of establishing the child's attitude to bedwetting prior to treatment is stressed.

Prognosis after grand mal seizures: a study of 187 children with three-year remissions.

From a total group of 640 children with grand mal seizures, 187 who became seizure-free for three consecutive years on monotherapy which was then discontinued have been followed for between one and 14 years. Relapse occurred in 22 children (12 per cent) and was related to age at presentation: only four of 89 children with primary grand mal seizures who had presented after the age of three years relapsed, compared with 12 of 45 who had presented before their third birthday. Children who had had more seizures were at greater risk of relapse. EEGs were not useful in predicting prognosis, whether taken at presentation or before withdrawal of treatment.

A comparison of two approaches to the treatment of nocturnal enuresis and the prediction of effectiveness using pre-treatment variables.

This study compared the effectiveness of the enuresis alarm alone with a brief version of Dry Bed Training in treating 74 enuretic children. Both procedures were equally effective, and in the total sample a better response to treatment was predicted by the child's report of being teased by siblings. Maternal anger was associated with a greater drop-out rate.

The medium chain triglyceride diet and intractable epilepsy.

Fifty children with drug resistant epilepsy were treated with the Medium Chain Triglyceride (MCT) Emulsion diet. Eight achieved complete control of seizures (four without anticonvulsant drugs), and with the addition of anticonvulsants four had seizures reduced in frequency by 90% and 10 by 50-90%. The best results were obtained with astatic myoclonic and absence seizures, but control of seizures was improved in four children with tonic-clonic and three with complex partial seizures. Food given at the same time as MCT helped to reduce side effects, and an extra dose of MCT before bedtime improved control of nocturnal seizures.

Role of octanoic and decanoic acids in the control of seizures.

Octanoic and decanoic acid, the major constituents of the Medium Chain Triglyceride (MCT) Emulsion diet, have been detected in appreciable quantities in the peripheral blood of children with intractable seizures treated with the MCT diet. Serum concentrations of these acids as well as beta hydroxybutyrate and acetoacetate rose as the diet was introduced and on full diet showed pronounced diurnal variation and low concentrations in the morning. No correlation between octanoic and decanoic acid concentrations and control of seizures was established, but further studies with octanoic and decanoic acid using animal models are necessary to assess the role of these acids and of control of seizures.

Bio-availability and dissolution of three phenytoin preparations for children.

A study of bio-availability of three drug companies' brands of phenytoin preparations (50mg capsule/tablets) was undertaken on 30 children with tonic-clonic or complex partial seizures. Eight children were excluded because of non-compliance and three because of abnormally high serum levels. Phenytoin capsules (Parke Davis) and tablets (Boots) produced significantly higher serum-level profiles than phenytoin tablets (Evans). Seizure frequencies did not differ significantly with the three brands of phenytoin. Dissolution of the three preparations tested in vitro was different. As a result of this study the authors recommend that children remain on the same manufacturer's brand of phenytoin throughout their treatment.

High-performance liquid chromatographic determination of carbamazepine and carbamazepine 10,11-epoxide in plasma and saliva following solid-phase sample extraction.

A rapid, sensitive and simple to operate high-performance liquid chromatographic method for the simultaneous determination of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) in plasma and saliva is described. The drug and its metabolite are extracted from both plasma and saliva using commercially available reversed-phase octadecylsilane bonded silica columns (Bond-Elut C18, 2.8 ml capacity). Separation of CBZ and CBZ-EP was achieved by reversed-phase chromatography, using a mobile phase consisting of acetonitrile-methanol-water (19:37:44) at a flow-rate of 1.8 ml/min in conjunction with a Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a Z-module RCSS and protected by a Guard-Pak precolumn module containing a Guard-Pak mu Bondapak C18 insert. Using ultraviolet detection at 214 nm, levels in the region of 50-100 ng/ml for CBZ and CBZ-EP can be measured with only 250 and 500 microliters of plasma and saliva, respectively. The method, which has been used to determine steady-state concentrations of the drug and its metabolite in paediatric patients receiving CBZ monotherapy, is also suitable for pharmacokinetic studies.

The cost of nutrition and diet therapy for low-income families.

The DHSS special dietary allowance system for those receiving supplementary benefit is explained. The cost of normal and common therapeutic diets are calculated. Inadequacies and shortcomings of the current dietary allowance are identified.

Solid-phase extraction of acetazolamide from biological fluids and subsequent analysis by high-performance liquid chromatography.

A sensitive, relatively fast and simple to operate high-performance liquid chromatographic method for the determination of acetazolamide in plasma and saliva is described. Quantitative extraction of the drug from both plasma and saliva was achieved using commercially available reversed-phase octadecylsilane-bonded silica column (Bond-Elut C18, 2.8 ml capacity). Acetazolamide and the internal standard are retained on the Bond-Elut C18 column and reproducibly recovered by elution with methanol. Liquid-liquid partition chromatography, carried out on a 30-cm mu Porasil column (10-microns porous silica) using a mobile phase consisting of dichloromethane-ethanol-water-glacial acetic acid (500:65:65:1), provided adequate separation with acceptable retention times. Acetazolamide levels in the region 50-100 ng/ml can be determined in 100 microliters of plasma or 200 microliters of saliva employing ultraviolet detection at 254 nm with a sensitivity of 0.005 absorbance units full scale. Although the method is primarily used to determine steady-state drug levels in paediatric patients, its general applicability is illustrated by the 24-h plasma and saliva concentration profiles obtained from a male volunteer following oral administration of acetazolamide.