Studies of water velocity in the capillary fringe: the point velocity probe.

The point velocity probe (PVP) is a device that can measure groundwater velocity at the centimeter scale, and unlike devices that measure velocity within well screens, the PVP operates while in direct contact with the porous medium. Because of this feature, it was postulated that the PVP could be effective in measuring velocity within the capillary fringe. This hypothesis was tested using a laboratory flow-through cell filled with a medium-fine sand from Canadian Forces Base Borden. The cell was constructed to simulate conditions such that the PVP was positioned from 2.5 cm below the water table to 79 cm above the water table. As the water table was lowered, the PVP gave highly consistent values of velocity over the range equivalent to 2.5 cm below the water table to 44 cm above the water table, the approximate extent of the capillary fringe. The average measured velocity was 11.3 cm/d +/- 11.6%, somewhat higher than that calculated based on the measured discharge through the cell (7.5 cm/d +/- 5.5%). With a further decline in the water table there was a progressive decrease in the measured velocity values, consistent with the declining hydraulic conductivity as the sand material drained. Readings could not be made beyond about 57 cm, where the water content was approximately 75% of saturation. These experiments showed that the PVP is capable of measuring groundwater velocity within the saturated zone above the water table and possibly into the unsaturated zone. Currently, this is the only instrument available with this capability.

Degradation of RDX using granular iron and nickel-plated granular iron.

Using granular iron (Fe) and nickel-plated iron (Ni/Fe), this paper examines the effectiveness of these two types of reactive materials for the treatment of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a common groundwater and soil contaminant at military facilities. RDX degraded very rapidly in the presence of both Fe and Ni/Fe in column and batch experiments. Enhancement by Ni/Fe did not prove to be effective as the half-lives of RDX ranged from 3 to 24 seconds and 3 to 11 seconds in the Fe and Ni/Fe columns, respectively. Reaction vessel experiments and estimation of the mass transfer coefficient in the column indicated that reaction kinetics was mass transfer limited. Detailed analyses of reaction intermediates and products suggest that RDX degradation proceeds through direct electron transfer processes and following to the same pathways in the presence of Fe and Ni/Fe. The formation of carbon-containing products, including formaldehyde (up to 60%), CO2 (up to 45%) and formic acid (1%) and the nitrogen containing products of ammonium (up to 48%) and N2O (up to 13%), provides convincing evidence that RDX was completely decomposed to non-toxic end products. CO2, previously reported to form only in biological or Fe-microbial combined systems, was detected as one of the main C-bearing end product. Therefore, this study shows that Fe is an effective material for remediating groundwater and industrial effluents containing RDX; and the use of additional enhancement, either biological or with Ni catalyst, does not provide additional advantages.

Influence of Na2S on the degradation kinetics of CCl4 in the presence of very pure iron.

This paper presents the results of kinetic studies to investigate the effect of FeS film formation on the degradation rate of CCl(4) by 99.99% pure metallic iron. The film was formed by submersing metallic iron grains in an oxygen free HCO(3)(-)/CO(3)(2-) electrolyte solution. When the grains had reached a quasi steady-state value of the corrosion potential, Na(2)S((aq)) was injected. Upon injection, a microm thick poorly crystalline FeS film formed immediately on the iron surface. Over time, the iron became strongly corroded and both the FeS film and the metallic iron grains began to crack leading to exposure of bare metallic iron to the solution. The effect of the surface film on the degradation rate of CCl(4) was investigated following four periods of aging, 1, 10, 30, and 60 days. Relative to the controls, the 1-day sulfide-aged iron showed a substantial decrease in rate of degradation of CCl(4.) However, over time, the rate of degradation increased and surpassed the degradation rate obtained in the controls. It has been proposed that CCl(4) is reduced to HCCl(3) by metallic iron by electron transfer. The FeS film is substantially less conducting than the bulk iron metal or non-stoichiometric magnetite and from the results of this study, greatly decreases the rate of CCl(4) degradation relative to iron that has not been exposed to Na(2)S. However, continued aging of the FeS film results in breakdown and stress-induced cracking of the film, followed by dissolution and cracking of the iron itself. The cracking of the bulk iron is believed to be a consequence of hydrogen embrittlement, which is promoted by sulfide. The increase in CCl(4) degradation rate, as the FeS films age, suggests that the process of hydrogen cracking increases the surface area available for charge transfer.

Probe for measuring groundwater velocity at the centimeter scale.

A novel method of measuring small-scale groundwater velocities in unconsolidated noncohesive media uses the travel time of a tracer pulse between an injection port and two detectors located on the surface of a cylindrical probe, called a point-velocity probe (PVP), as the basis for velocity estimation. The direction and magnitude of the water velocity vector were determined to within +/- 9% of magnitude and +/- 8 in direction, on average, in ten laboratory tank tests conducted with the PVP, when the velocities were between 5 and 98 cm/ day. Numerical simulations supported the accuracy of the underlying theory for interpretation of the PVP data and indicated that the technology is capable of measuring velocity at a very fine scale (0.5 cm around the circumference). The benchtop and modeling investigations indicated that the probe is moderately sensitive to the condition of the porous medium immediately next to the cylinder surface, suggesting that challenges exist for the deployment of the instrument in the field.

Laboratory evidence of natural remobilization of multicomponent DNAPL pools due to dissolution.

Mixtures of dense non-aqueous phase liquids (DNAPLs) trapped in the subsurface can act as long-term sources of contamination by dissolving into flowing groundwater. In general, the components of higher solubility are removed more quickly, thus altering the composition of the remaining DNAPL, and possibly leading to changes in its physical properties. Through the development of a simple compositional model, Roy et al. [J. Contam. Hydrol. 2002 (59) 163] showed that preferential dissolution of a mixed DNAPL could potentially result in changes in density and interfacial tension that could subsequently lead to remobilization of an initially static DNAPL pool. The laboratory experiments presented in this next paper provide a proof-of-concept for the previously presented theory, demonstrating and quantifying this process of remobilization. In addition, the experiments provide a data set for evaluation of the model presented by Roy et al. [J. Contam. Hydrol. 2002 (59) 163]. In the four experiments, a DNAPL pool comprised of tetrachloroethene and benzene was created as an open pool overlying glass beads within a water-saturated 2-D flow box. Experiments included rectangular and triangular pools. In each of the experiments, remobilization (as breakthrough) was observed more than 2 weeks after formation of the initial pool. During each experiment, the pool height declined as mass was lost by dissolution, while sampling indicated a decrease in the mole fraction of benzene, the more soluble component. Small protuberances formed along the bottom of the pool as its composition changed with time and the displacement pressure was achieved for various pore throats. Eventually one of the protuberances extended further, forming a finger (breakthrough). In general, the pool emptied as the finger proceeded further into the beads. It was also shown theoretically and experimentally that remobilization will occur sooner for pools with a triangular (pointing down), rather than rectangular, shape. The experimental results were simulated using the model developed by Roy et al. [J. Contam. Hydrol. 2002 (59) 163]. The model matched the observations well, suggesting that it accurately represents the primary mechanisms involved with natural remobilization under the conditions of the study.

A sequential zero valent iron and aerobic biodegradation treatment system for nitrobenzene.

The remediation of nitroaromatic contaminated groundwater is sometimes difficult because nitroaromatic compounds are resistant to biodegradation and, when they do transform, the degradation of the products may also be incomplete. A simple nitroaromatic compound, nitrobenzene, was chosen to assess the feasibility of an in situ multi-zone treatment system at the laboratory scale. The proposed treatment system consists of a zero valent granular iron zone to reduce nitrobenzene to aniline, followed by a passive oxygen release zone for the aerobic biodegradation of the aniline daughter product using pristine aquifer material from Canadian Forces Base (CFB) Borden, Ontario, as an initial microbial source. In laboratory batch experiments, nitrobenzene was found to reduce quickly in the presence of granular iron forming aniline, which was not further degraded but remained partially sorbed onto the granular iron surface. Aniline was found to be readily biodegraded with little metabolic lag under aerobic conditions using the pristine aquifer material. A sequential column experiment, containing a granular iron reducing zone and an aerobic biodegradation zone, successively degraded nitrobenzene and then aniline to below detection limits (0.5 microM) without any noticeable reduction in hydraulic conductivity from biofouling, or through the formation of precipitates.

An in situ study of the effect of nitrate on the reduction of trichloroethylene by granular iron.

The effect of nitrate on the reduction of TCE by commercial granular iron was investigated in column experiments designed to allow for the in situ monitoring of the iron surface film with Raman spectroscopy. Three column experiments were conducted; one with an influent solution of 100 mg/l nitrate+1.5 mg/l TCE, and two control columns, one saturated directly with 100 mg/l nitrate solution, the other pre-treated with Millipore water prior to the introduction of a 100 mg/l nitrate solution. In the presence of nitrate, TCE adsorbed onto the iron, but there was little TCE reduction to end-products ethene and ethane. The iron used (Connelly, GPM, Chicago) is a product typical of those used in permeable granular iron walls. The material is covered by an air-formed high-temperature oxidation film, consisting of an inner layer of Fe(3)O(4), and an outer, passive layer of Fe(2)O(3). In the control column pre-treated with Millipore water, the passive Fe(2)O(3) layer was removed upon contact with the water in a manner consistent with an autoreduction reaction. In the TCE+nitrate column and the direct nitrate saturation column, nitrate interfered with the removal of the passive layer and maintained conditions such that high valency protective corrosion species, including Fe(2)O(3) and FeOOH, were stable at the iron surface. The lack of TCE reduction is explained by the presence of these species, as they inhibit both mechanisms proposed for TCE reduction by iron, including catalytic hydrogenation, and direct electron transfer.

A fatal waterborne disease epidemic in Walkerton, Ontario: comparison with other waterborne outbreaks in the developed world.

An estimated 2,300 people became seriously ill and seven died from exposure to microbially contaminated drinking water in the town of Walkerton, Ontario, Canada in May 2000. The severity of this drinking water disaster resulted in the Government of Ontario calling a public inquiry by Mr. Justice Dennis O'Connor to address the cause of the outbreak, the role (if any) of government policies in contributing to this outbreak and, ultimately, the implications of this experience on the safety of drinking water across the Province of Ontario. The circumstances surrounding the Walkerton tragedy are an important reference source for those concerned with providing safe drinking water. Although some circumstances are obviously specific to this epidemic, others are uncomfortably reminiscent of waterborne outbreaks that have occurred elsewhere. These recurring themes suggested the need for attention to broad issues of drinking water security and they present the challenge for how drinking water safety can be managed to prevent such tragedies in the future.

Natural remobilization of multicomponent DNAPL pools due to dissolution.

Mixtures of dense nonaqueous phase liquids (DNAPLs) trapped in the subsurface can act as long-term sources of contamination by dissolving into flowing groundwater. If the components have different solubilities then dissolution will alter the composition of the remaining DNAPL. We theorized that a multicomponent DNAPL pool may become mobile due to the natural dissolution process. In this study, we focused on two scenarios: (1) a DNAPL losing light component(s), with the potential for downward migration; and (2) a DNAPL losing dense component(s), with the potential for upward migration following transformation into a less dense than water nonaqueous phase liquid (LNAPL). We considered three binary mixtures of common groundwater contaminants: benzene and tetrachloroethylene (PCE), PCE and dichloromethane (DCM), and DCM and toluene. A number of physical properties that control the retention and transport of DNAPL in porous media were measured for the mixtures, namely: density, interfacial tension, effective solubility, and viscosity. All properties except density exhibited nonlinear relationships with changing molar ratio of the DNAPL. To illustrate the potential for natural remobilization, we modelled the following two primary mechanisms: the reduction in pool height as mass is lost by dissolution, and the changes in fluid properties with changing molar ratio of the DNAPL. The first mechanism always reduces the capillary pressure in the pool, while the second mechanism may increase the capillary pressure or alter the direction of the driving force. The difference between the rate of change of each determines whether the potential for remobilization increases or decreases. Static conditions and horizontal layering were assumed along with a one-dimensional, compositional modelling approach. Our results indicated that for initial benzene/PCE ratios greater than 25:75, the change in density was sufficiently faster than the decline in pool height to promote DNAPL breakthrough into the adjacent porous medium. In contrast, there was no potential for natural remobilization of a PCE-DCM mixture, primarily because the densities of the components are not sufficiently different. Dissolution of a DCM-toluene mixture decreased the density, reducing the tendency for downward displacement. However, the ultimate transformation from a DNAPL to an LNAPL may induce upward displacement. These results suggest that at sites with DNAPL pools containing a mix of components of sufficiently different densities and relative solubilities, natural remobilization may be an active mechanism, with implications for site evaluation and remediation.

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.

An in situ study of the role of surface films on granular iron in the permeable iron wall technology.

Permeable walls of granular iron are a new technology developed for the treatment of groundwater contaminated with dissolved chlorinated solvents. Degradation ofthe chlorinated solvents involves a charge transfer process in which they are reductively dechlorinated, and the iron is oxidized. The iron used in the walls is an impure commercial material that is covered with a passive layer of Fe2O3, formed as a result of a high-temperature oxidation process used in the production of iron. Understanding the behaviour of this layer upon contact with solution is important, because Fe2O3 inhibits mechanisms involved in contaminant reduction, including electron transfer and catalytic hydrogenation. Using a glass column specially designed to allow for in situ Raman spectroscopic and open circuit potential measurements, the passive layer of Fe2O3 was observed to be largely removed from the commercial product, Connelly iron, upon contact with Millipore water and with a solution of Millipore water containing 1.5 mg/l trichloroethylene (TCE). It has been previously shown that Fe2O3 is removed from iron surfaces upon contact with solution by an autoreduction reaction; however, prior to this work, the reaction has not been shown to occur on the impure commercial iron products used in permeable granular iron walls. The rate of removal was sufficiently rapid such that the initial presence of Fe2O3 at the iron surface would have no consequence with respect to the performance of an in situ wall. Subsequent to the removal of Fe2O3 layer, magnetite and green rust formed at the iron surface as a result of corrosion in both the Millipore water and the solution containing TCE. The formation of these two species, rather than higher valency iron oxides and oxyhydroxides, is significant for the technology. The former can interfere with contaminant degradation because they inhibit electron transfer and catalytic hydrogenation. Magnetite and green rust, in contrast, will not inhibit the mechanisms involved in contaminant reduction, and hence their formation is beneficial to the long-term performance of the iron material.

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers.

OBJECTIVES: To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy. METHODS: The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests. RESULTS: Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers. CONCLUSIONS: The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.

Validation of the side effect and life satisfaction (SEALS) inventory.

Diminished quality of life (QOL) is a common feature of epilepsy. It is generally more severe among patients with poor seizure control but prevalent, to a clinically significant degree, even among those whose seizures are well controlled. People with epilepsy frequently report diminished socialization, negative self image, feelings of stigmatization, reduced earnings potential, and diminished hope and ambition. Problems with antiepileptic drug (AED) therapy are common, and AED therapy is recognized as an important determinant of health-related quality of life (HRQOL). A clinically efficient psychometric instrument is needed to measure its impact. The Side Effect and Life Satisfaction (SEALS) inventory is a 38-item, patient-completed questionnaire designed to measure satisfaction with AED therapy. We tested its construct validity in comparison with three widely used psychometric instruments of similar design, the Profile of Mood States (POMS), the Hospital Anxiety and Depression (HAD) scale, and the Medical Outcomes Study-Cognitive Functioning (MOS-COG) scale. All four instruments were completed by 307 epilepsy patients. A matrix of Pearson's correlations was produced for the SEALS inventory and the comparative instruments. A statistically significant correlation was found for each planned comparison. We conclude that the SEALS inventory is a valid psychometric instrument, well suited for use in clinical investigations of AED therapy and in the practical, long-term management of epilepsy.

A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure.

The aim of this study was to compare the effect of treatment with lamotrigine (LTG) or carbamazepine (CBZ) on health-related quality of life (HRQOL) and to demonstrate the use of the SEALS Inventory as a comparative tool in clinical trials. Two hundred and sixty patients with newly diagnosed epilepsy were randomized to 48 weeks of treatment with LTG (n = 131) or CBZ (n = 129). HRQOL was measured at baseline and weeks 4, 12, 24, and 48 using the modified Side Effect and Life Satisfaction (SEALS) Inventory-a 38-item questionnaire divided into five subscales: Worry, Temper, Cognition, Dysphoria, and Tiredness. Overall, SEALS scores in the LTG group decreased (improved) significantly from baseline (P = 0.001). The LTG group had improvement in all five subscales over the 48 weeks of the study. CBZ patients had significantly worse SEALS scores than LTG patients at week 4 (P < 0.038). There was no significant change (positive or negative) in subsequent SEALS assessments. Analysis of SEALS data by subscale showed that the the CBZ group experienced more cognitive side-effects in general and more general changes in energy levels and affect during the first 4 weeks of treatment. These changes may help explain the difference in study completion rate: LTG 65%, CBZ 51% (P = 0.018). LTG offers the patient with newly diagnosed epilepsy significant benefits of greater tolerability and better health-related quality of life compared with CBZ. The SEALS Inventory is an effective tool for use in clinical trials of AEDs; it was a better predictor of trial completion than seizure counts, and used as a covariate enabled better detection of treatment effects. In general practice, the use of the SEALS Inventory to assess HRQOL has the potential to improve quality of care for people with epilepsy.

Long-term performance monitoring for a permeable reactive barrier at the U.S. Coast Guard Support Center, Elizabeth City, North Carolina.

A continuous hanging iron wall was installed in June, 1996, at the U. S. Coast Guard (USCG) Support Center near Elizabeth City, NC, United States, to treat overlapping plumes of chromate and chlorinated solvent compounds. The wall was emplaced using a continuous trenching machine whereby native soil and aquifer sediment was removed and the iron simultaneously emplaced in one continuous excavation and fill operation. To date, there have been seven rounds (November 1996, March 1997, June 1997, September 1997, December 1997, March 1998, and June 1998) of performance monitoring of the wall. At this time, this is the only full-scale continuous 'hanging' wall installed as a permeable reactive barrier to remediate both chlorinated solvent compounds and chromate in groundwater. Performance monitoring entails the following: sampling of 10-5 cm PVC compliance wells and 15 multi-level samplers for the following constituents: TCE, cis-dichloroethylene (c-DCE), vinyl chloride, ethane, ethene, acetylene, methane, major anions, metals, Cr(VI), Fe(II), total sulfides, dissolved H(2), Eh, pH, dissolved oxygen, specific conductance, alkalinity, and turbidity. Electrical conductivity profiles have been conducted using a Geoprobe to verify emplacement of the continuous wall as designed and to locate upgradient and downgradient wall interfaces for coring purposes. Coring has been conducted in November, 1996, in June and September, 1997, and March, 1998, to evaluate the rate of corrosion on the iron surfaces, precipitate buildup (particularly at the upgradient interface), and permeability changes due to wall emplacement. In addition to several continuous vertical cores, angled cores through the 0.6-m thick wall have been collected to capture upgradient and downgradient wall interfaces along approximate horizontal flow paths for mineralogic analyses.

Regional cerebral perfusion and amytal distribution during the Wada test.

UNLABELLED: The distribution of sodium amytal and its effect on regional cerebral perfusion during the intracarotid amytal (Wada) test were investigated using high-resolution hexamethyl propyleneamine oxime (HMPAO) SPECT coregistered with the patient's MRI dataset. METHODS: Twenty patients underwent SPECT after intravenous HMPAO injection, and 5 patients had both intravenous and intracarotid injections in a double injection-acquisition protocol. RESULTS: All patients had hypoperfusion in the territories of the anterior and middle cerebral arteries. Basal ganglia perfusion was preserved in 20 of 25 patients. Hypoperfusion of the entire mesial temporal cortex was seen in 9 of 25 patients. Partial hypoperfusion of the whole mesial cortex or hypoperfusion of part of the mesial cortex was seen in 14 of 25 patients. In 2 of 25 patients, mesial temporal perfusion was unaffected. In 5 patients, the double acquisition showed a distribution of HMPAO delivery matching that of hypoperfusion, except for the following: (a) HMPAO was delivered to the basal ganglia and insula, where there was no hypoperfusion; (b) HMPAO was not delivered to the contralateral cerebellum, which did show hypoperfusion; and (c) in 1 patient, perfusion of the mesial temporal cortex was preserved despite intracarotid delivery of HMPAO. CONCLUSION: Some degree of hypoperfusion of medial temporal structures occurs in the great majority of patients during the Wada test. Partial inactivation of memory structures is therefore a credible mechanism of action of the test. The double acquisition protocol provided no evidence that mesial temporal structures are inactivated remotely by diaschisis. Perfusion in the basal ganglia and insular cortex is not affected by amytal.

Standardisation of a self-report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments.

The development and standardisation of an inventory for measuring anti-epileptic drug effects on cognition and affect is described. The Side Effect and Life Satisfaction inventory (SEALS) was derived from symptoms and side-effects reported by a patient population. It was administered to 45 patients on two occasions and test-retest reliability was demonstrated. It was administered to 923 patients with epilepsy. An underlying factor structure was produced by principal components analysis, consisting of five sub-scales which were stable when data from males and females were analysed separately or together. Validity was evaluated by comparing inventory scores of patients undergoing a number of treatment trials to show that the inventory was sensitive to treatment differences when other variables were controlled. Patients taking two or more anti-epileptic drugs had poorer SEALS scores than those taking a single drug. Patients taking vigabatrin and one other AED had poorer scores than those taking lamotrigine (LTG) and one other AED. A comparison of changes from baseline to week 4 of a double blind comparison of carbamazepine (CBZ) and LTG showed significantly greater improvement in SEALS scores for patients taking LTG, and significantly poorer scores in those patients taking CBZ who dropped out of the study, than in those who continued. It is concluded that SEALS is a valid and reliable tool for use in anti-epileptic drug trials.

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.

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.