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T W May

Publications and source records attributed to T W May.

At least 19 recordsLinked to original sources
PubMed2003

[Is epilepsy in the elderly overlooked? An investigation in a home for the aged].

The symptoms of epileptic seizures in old patients differ from those in younger patients. Therefore, these seizures may be misinterpreted as symptoms of other "typical" diseases in old people. In an old people's home, we assessed whether a standardized questionnaire is able to reveal undiagnosed epilepsy in the elderly. Reported sudden falls, loss of consciousness, and cramps were the criteria for further diagnostic procedures. We found epilepsy in 11 of 389 study participants. In four of them (1% of the total sample), the epilepsy was newly diagnosed; five more cases remained unclear. Therefore, the total number of epileptic patients might have been even higher. Most of the reported sudden falls and unconsciousness (89%) were due to internal medical or other neurological or orthopaedic causes. Once these have been excluded, the diagnosis of epilepsy should be considered. The results of our pilot study suggest that epilepsy in old people's homes is often unrecognised. Early diagnosis and treatment of epilepsy in the elderly is important to improve prognosis and social consequences for affected persons.

Accidental Falls↗
PubMed2002

Toxicity assessment of sediments from the Grand Calumet River and Indiana Harbor Canal in Northwestern Indiana, USA.

The objective of this study was to evaluate the toxicity of sediments from the Grand Calumet River and Indiana Harbor Canal located in northwestern Indiana, USA. Toxicity tests used in this assessment included 10-day sediment exposures with the amphipod Hyalella azteca, 31-day sediment exposures with the oligochaete Lumbriculus variegatus, and the Microtox Solid-Phase Sediment Toxicity Test. A total of 30 sampling stations were selected in locations that had limited historic matching toxicity and chemistry data. Toxic effects on amphipod survival were observed in 60% of the samples from the assessment area. Results of a toxicity test with oligochaetes indicated that sediments from the assessment area were too toxic to be used in proposed bioaccumulation testing. Measurement of amphipod length after the 10-day exposures did not provide useful information beyond that provided by the survival endpoint. Seven of the 15 samples that were identified as toxic in the amphipod tests were not identified as toxic in the Microtox test, indicating that the 10-day H. azteca test was more sensitive than the Microtox test. Samples that were toxic tended to have the highest concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs). The toxic samples often had an excess of simultaneously extracted metals (SEM) relative to acid volatile sulfide (AVS) and had multiple exceedances of probable effect concentrations (PECs). Metals may have contributed to the toxicity of samples that had both an excess molar concentration of SEM relative to AVS and elevated concentrations of metals in pore water. However, of the samples that had an excess of SEM relative to AVS, only 38% of these samples had elevated concentration of metals in pore water. The lack of correspondence between SEM-AVS and pore water metals indicates that there are variables in addition to AVS controlling the concentrations of metals in pore water. A mean PEC quotient of 3.4 (based on concentrations of metals, PAHs, and PCBs) was exceeded in 33% of the sediment samples and a mean quotient of 0.63 was exceeded in 70% of the thirty sediment samples from the assessment area. A 50% incidence of toxicity has been previously reported in a database for sediment tests with H. azteca at a mean quotient of 3.4 in 10-day exposures and at a mean quotient of 0.63 in 28-day exposures. Among the Indiana Harbor samples, most of the samples with a mean PEC quotient above 0.63 ( i.e., 15 of 21; 71%) and above 3.4 ( i.e., 10 of 10; 100%) were toxic to amphipods. Results of this study and previous studies demonstrate that sediments from this assessment area are among the most contaminated and toxic that have ever been reported.

Animals↗
PubMed2001

Influence of mining-related activities on concentrations of metals in water and sediment from streams of the Black Hills, South Dakota.

Water and sediment samples were collected from streams in Spearfish Creek, Whitewood Creek, and Bear Butte Creek watersheds in the Black Hills, SD, an area impacted by gold mining operations. Arsenic concentrations that exceeded the U.S. Environmental Protection Agency's Maximum Concentration Limit of 50 microg/L for drinking water were found in water from Annie Creek, a tributary of Spearfish Creek, and from Whitewood Creek. Gold Run, a tributary of Whitewood Creek, and Annie Creek contained Se concentrations in water that exceeded the EPA Ecotox threshold of 5 microg/L and were classified as a high hazard for Se accumulation from water into the planktonic food chain and for resultant toxicity to fish and aquatic birds. Concentrations of As, Cd, Cu, Hg, Ni, Pb, and Zn in sediment exceeded EPA Ecotox thresholds in one or more of the watersheds suggesting potential adverse ecological effects. Sediment from Rubicon Creek, a tributary of Spearfish Creek, contained Se concentrations high enough (4.0 microg/g) to be a moderate hazard for accumulation from sediments into the benthic food chain, with resultant dietary toxicity to fish and aquatic birds. These results are discussed in light of historical mining activities and recent clean-up and reclamation efforts. Based on the results and comparisons to Ecotox tresholds, further studies of ecological effects are warranted.

Environmental Monitoring↗
PubMed2001

Bioavailability of metals in stream food webs and hazards to brook trout (Salvelinus fontinalis) in the upper Animas River watershed, Colorado.

The water quality, habitats, and biota of streams in the upper Animas River watershed of Colorado, USA, are affected by metal contamination associated with acid drainage. We determined metal concentrations in components of the food web of the Animas River and its tributaries-periphyton (aufwuchs), benthic invertebrates, and livers of brook trout (Salvelinus fontinalis)-and evaluated pathways of metal exposure and hazards of metal toxicity to stream biota. Concentrations of the toxic metals cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) in periphyton, benthic invertebrates, and trout livers from one or more sites in the upper Animas River were significantly greater than those from reference sites. Periphyton from sites downstream from mixing zones of acid and neutral waters had elevated concentrations of aluminum (Al) and iron (Fe) reflecting deposition of colloidal Fe and Al oxides, and reduced algal biomass. Metal concentrations in benthic invertebrates reflected differences in feeding habits and body size among taxa, with greatest concentrations of Zn, Cu, and Cd in the small mayfly Rhithrogena, which feeds on periphyton, and greatest concentrations of Pb in the small stonefly Zapada, a detritivore. Concentrations of Zn and Pb decreased across each trophic linkage, whereas concentrations of Cu and Cd were similar across several trophic levels, suggesting that Cu and Cd were more efficiently transferred via dietary exposure. Concentrations of Cu in invertebrates and trout livers were more closely associated with impacts on trout populations and invertebrate communities than were concentrations of Zn, Cd, or Pb. Copper concentrations in livers of brook trout from the upper Animas River were substantially greater than background concentrations and approached levels associated with reduced brook trout populations in field studies and with toxic effects on other salmonids in laboratory studies. These results indicate that bioaccumulation and transfer of metals in stream food webs are significant components of metal exposure for stream biota of the upper Animas River watershed and suggest that chronic toxicity of Cu is an important factor limiting the distribution and abundance of brook trout populations in the watershed.

Animals↗
PubMed2001

An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Republican River Basin: 1997-1999.

The Republican River Basin of Colorado, Nebraska, and Kansas lies in a valley which contains Pierre Shale as part of its geological substrata. Selenium is an indigenous constituent in the shale and is readily leached into surrounding groundwater. The Basin is heavily irrigated through the pumping of groundwater, some of which is selenium-contaminated, onto fields in agricultural production. Water, sediment, benthic invertebrates, and/or fish were collected from 46 sites in the Basin and were analyzed for selenium to determine the potential for food-chain bioaccumulation, dietary toxicity, and reproductive effects of selenium in biota. Resulting selenium concentrations were compared to published guidelines or biological effects thresholds. Water from 38% of the sites (n = 18) contained selenium concentrations exceeding 5 microg L(-1), which is reported to be a high hazard for selenium accumulation into the planktonic food chain. An additional 12 sites (26% of the sites) contained selenium in water between 3-5 microg L(-1), constituting a moderate hazard. Selenium concentrations in sediment indicated little to no hazard for selenium accumulation from sediments into the benthic food chain. Ninety-five percent of benthic invertebrates collected exhibited selenium concentrations exceeding 3 microg g(-1), a level reported as potentially lethal to fish and birds that consume them. Seventy-five percent of fish collected in 1997, 90% in 1998, and 64% in 1999 exceeded 4 microg g(-1) selenium, indicating a high potential for toxicity and reproductive effects. However, examination of weight profiles of various species of collected individual fish suggested successful recruitment in spite of selenium concentrations that exceeded published biological effects thresholds for health and reproductive success. This finding suggested that universal application of published guidelines for selenium may be inappropriate or at least may need refinement for systems similar to the Republican River Basin. Additional research is needed to determine the true impact of selenium on fish and wildlife resources in the Basin.

Animals↗
PubMed2001

Incidence of epilepsies and epileptic syndromes in children and adolescents: a population-based prospective study in Germany.

PURPOSE: To estimate the incidence rate of epilepsies and epileptic syndromes in German children and adolescents aged 1 month to <15 years, and to provide data on their classification. METHODS: A population-based prospective study was performed between July 1, 1999, and June 30, 2000. All children aged 1 month to <15 years with a newly diagnosed epilepsy or epileptic syndrome were recorded by private pediatricians, EEG laboratories, and the two University Children's Hospitals in the neighboring cities of Heidelberg and Mannheim. The diagnoses were classified according to the International Classification of Epilepsies and Epileptic Syndromes of the International League Against Epilepsy (ILAE). RESULTS: The total age-adjusted annual incidence rate was 60/100,000 (95% confidence interval, 42-84), with the highest incidence in the first year of life (146/100,000). Focal epilepsies or epileptic syndromes (58%; incidence rate, 35/100,000) were more common than were generalized ones (39%; incidence rate, 24/100,000), and 3% (incidence rate, 2/100,000) of the epilepsies or epileptic syndromes were undetermined. The rate of idiopathic (47%; incidence rate, 29/100,000) and symptomatic or cryptogenic epilepsies (50%; incidence rate, 30/100,000) was equal. No significant difference in incidence between boys and girls was found. CONCLUSIONS: Incidence rates for epilepsy in German children aged 1 month to <15 years are about equal to those of other countries in Europe and North America. In accordance with studies from the United States and from many European countries, incidence was highest in the first year of life, and no difference in the incidence between girls and boys was found. In Germany as throughout Europe, idiopathic generalized epileptic syndromes are more often diagnosed than in the United States.

Adolescent↗
PubMed2000

Is geomagnetic activity a risk factor for sudden unexplained death in epilepsies?

OBJECTIVE: To test the hypothesis that sudden unexplained death (SUD) in epilepsy is related to geomagnetic activity. BACKGROUND: Prior studies presume that geomagnetic activity (with average amplitudes above 50 nanotesla [nT]) is associated with SUD in epileptic human patients and in epileptic laboratory rats. METHODS: In a retrospective study, 46 epileptic patients with definite SUD were compared with 108 epileptic patients with known cause of death (KCD) who died between 1981 and 1992. A complete postmortem examination was performed in all cases. The time of the day and date of death, as well as two international geomagnetic indices concerning Bartels' planetary 3-hour signs (Kp) and the mean planetary daily amplitudes (Ap) at time of death, were assessed. RESULTS: Among 45 SUD individuals, the local time (37.8%) and the universal time of death (35.6%) peaked within the critical period between 3 to 9 AM. However, the SUD and KCD group did not substantially differ in regard to the distribution of local or universal time of death (p > 0.2, Fisher test). Neither the Kp signs at death and 2 hours before death nor the Ap values showed considerable differences between the SUD and KCD series (p > 0.2, Mann-Whitney test). Merely 4.3% of SUD patients and 3.7% of KCD patients were associated with Ap indices above 50 nT (p > 0.2, Fisher test). CONCLUSION: The results do not support the hypothesis that geomagnetic activity is related to occurrence of sudden unexplained death in epileptic patients.

Adult↗
PubMed2000

Hazard assessment of selenium and other trace elements in wild larval razorback sucker from the Green River, Utah.

Contaminant investigations of the Green River in northeastern Utah have documented selenium contamination at sites receiving irrigation drainage. The Green River provides critical habitat for four endangered fishes including the largest extant riverine population of endangered razorback sucker. Although 2175 larval razorback suckers were collected from the river between 1992 and 1996, very few juveniles have been captured within recent decades. Selenium concentrations were measured in larval razorback suckers collected from five sites in the Green River (Cliff Creek, Stewart Lake Drain, Sportsman's Drain, Greasewood Corral, and Old Charlie Wash) to assess the potential for adverse effects on recruitment of larvae to the juvenile stage and the adult population. Larvae from all sites contained mean selenium concentrations ranging from 4.3 to 5.8 microg/g. These values were at or above the proposed toxic threshold of 4 microg/g for adverse biological effects in fish, which was derived from several laboratory and field studies with a wide range of fish species. At two sites, Cliff Creek and Stewart Lake Drain, selenium concentrations in larvae increased over time as fish grew, whereas selenium concentrations decreased as fish grew at Sportsman's Drain. Evaluation of a 279-larvae composite analyzed for 61 elements demonstrated that selenium and, to a lesser extent, vanadium were elevated to concentrations reported to be toxic to a wide range of fish species. Elevated selenium concentrations in larval razorback suckers from the five sites suggest that selenium contamination may be widespread in the Green River, and that survival and recruitment of larvae to the juvenile stage may be limited due to adverse biological effects. Selenium contamination may be adversely affecting the reproductive success and recruitment of endangered razorback sucker.

Animals↗
PubMed2000

Selenium concentrations in the Colorado pikeminnow (Ptychocheilus lucius): relationship with flows in the upper Colorado River.

A Department of the Interior (DOI) irrigation drainwater study of the Uncompahgre Project area and the Grand Valley in western Colorado revealed high selenium concentrations in water, sediment, and biota samples. The lower Gunnison River and the Colorado River in the study area are designated critical habitat for the endangered Colorado pikeminnow (Ptychocheilus lucius) and razorback sucker (Xyrauchen texanus). Because of the endangered status of these fish, sacrificing individuals for tissue residue analysis has been avoided; consequently, little information existed regarding selenium tissue residues. In 1994, muscle plugs were collected from a total of 39 Colorado pikeminnow captured at various Colorado River sites in the Grand Valley for selenium residue analysis. The muscle plugs collected from 16 Colorado pikeminnow captured at Walter Walker State Wildlife Area (WWSWA) contained a mean selenium concentration of 17 microg/g dry weight, which was over twice the recommended toxic threshold guideline concentration of 8 microg/g dry weight in muscle tissue for freshwater fish. Because of elevated selenium concentrations in muscle plugs in 1994, a total of 52 muscle plugs were taken during 1995 from Colorado pikeminnow staging at WWSWA. Eleven of these plugs were from fish previously sampled in 1994. Selenium concentrations in 9 of the 11 recaptured fish were significantly lower in 1995 than in 1994. Reduced selenium in fish may in part be attributed to higher instream flows in 1995 and lower water selenium concentrations in the Colorado River in the Grand Valley. In 1996, muscle plugs were taken from 35 Colorado squawfish captured at WWSWA, and no difference in mean selenium concentrations were detected from those sampled in 1995. Colorado River flows during 1996 were intermediate to those measured in 1994 and 1995.

Animals↗
PubMed1999

Organochlorine residues and elemental contaminants in U.S. freshwater fish, 1976-1986: National Contaminant Biomonitoring Program.

As part of the National Contaminant Biomonitoring Program (NCBP, formerly a component of the National Pesticide Monitoring Program), the U.S. Fish and Wildlife Service periodically determined concentrations of organochlorine chemical residues and elemental contaminants in freshwater fish collected from a nationwide network of stations. In late 1986 and early 1987, the last time the network was sampled, a total of 319 composite fish samples were collected from 97 NCBP stations. The samples were analyzed for residues of organochlorine chemicals and the elements As, Cd, Cu, Hg, Pb, Se, and Zn. The mean concentration of total DDT and its homologs (p,p'-constituents) declined from 1984 to 1986, thus continuing a trend that began in 1970. The most persistent DDT homolog (p,p'-DDE) was detected at all stations sampled in 1986, and averaged 74% of total DDT residues, up from 70% in 1974-1979 but essentially unchanged from 1984. Collectively, these findings indicated a low rate of influx and continued weathering of DDT in the environment; nevertheless, DDT concentrations in fish from some stations in the South remained high enough to constitute a threat to piscivorous wildlife. Residues of polychlorinated biphenyls (PCBs) also remained widespread, but a significant downward trend in total PCB concentrations and incidence was evident, and PCB mixtures containing early eluting components were present at fewer stations than in the past. PCB concentrations were generally highest in fish from the industrialized rivers of the Northeast and Midwest and from the Great Lakes. Concentrations of toxaphene also declined, as did its incidence, from 88% of the stations sampled in 1980-1981 to 64% in 1986; however, analytical problems with the 1986 samples may have contributed to the latter. The risks represented by PCBs and toxaphene could not be evaluated on the basis of our data. Among cyclodiene insecticides, dieldrin and chlordane-related residues were the most widespread. Mean concentrations of dieldrin declined through 1986, but remained consistently highest in the Great Lakes. For chlordane-related residues, mean concentrations were lower that reported previously, and trans-nonachlor continued to replace cis-chlordane as the most abundant component. Collectively, these findings suggested a lower rate of chlordane influx to the aquatic environment; however, a point source of cyclodiene insecticides to the Mississippi R. near Memphis, TN, remained evident. Residues of mirex, PCA, BHC isomers, endrin, heptachlor, and HCB were either found at relatively few (< 25%) of the stations sampled in 1986 or were characterized by relatively low concentrations. Concentrations of the herbicide Dacthal (DCPA) were also low, but incidence increased from 46% of the stations sampled in 1984 to 61% in 1986. In general, organochlorine chemical concentrations were lower in 1986 than at any time reported previously. For elemental contaminants, the geometric mean, maximum, and 85th percentile concentrations (respectively, all in microgram/g wet weight) in 1986 samples were as follows: As, 0.083, 1.53, 0.24; Cd, 0.011, 0.32, 0.04; Cu, 0.794, 11.0, 1.7; Hg, 0.087, 0.44, 0.18; Pb, 0.058, 1.90, 0.21; Se, 0.417, 3.41, 0.66; and Zn, 21.191, 94.5, 31.7. Mean concentrations of Cu increased and concentrations of As decreased relative to the 1984 collection, but these changes may reflect subtle differences in the species composition of the 1986 collection relative to other collections; concentrations of both elements differ greatly among fishes. There were no other statistically significant changes from 1984 to 1986; however, mean concentrations of As, Cd, Pb, and Zn declined from 1976, when elemental contaminants in fish were first measured in the NCBP, and 1986. In contrast, mean concentrations of Hg and Se did not change appreciably. Moreover, and in contrast to the other elements measured in 1986, concentrations of Hg and Se were high enough to constitute a threat to pisc

Animals↗
PubMed1999

Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study.

The aim of this retrospective study was to investigate the influence of oxcarbazepine (OCBZ) and methsuximide (MSM) on lamotrigine (LTG) serum concentrations. The effect of OCBZ compared to carbamazepine (CBZ) and the effect of MSM on LTG serum concentrations were examined in patients with and without valproic acid (VPA) comedication. Altogether, 376 samples from 222 patients were analyzed in routine drug monitoring. Two or more serum samples from the same patient were considered only if the comedication had been changed. For statistical evaluation, regression analytical methods and an analysis of variance were performed. For the analysis of variance, the LTG serum concentration in relation to LTG dose/ body weight--level-to-dose ratio (LDR), in (microg/mL)/(mg/kg)--was calculated and compared for different drug combinations. The nonlinear regression analysis including the LTG dose per body weight, age, gender, and the different kinds of comedication revealed that these variables have a significant influence on LTG serum concentration (r2 = 0.724). The relationship between LTG dose/body weight and serum concentration deviates only slightly from linearity, the LTG concentration was about 18% lower in women than in men, and age had a significant influence. The data indicate that children have significantly lower LTG concentrations than adults on a comparable LTG dose per body weight and that children may be more prone to enzyme induction by comedicated drugs. Methsuximide has a strong inducing effect on the LTG metabolism and decreases the LTG concentrations markedly (about 70% compared to LTG monotherapy). Carbamazepine also reduces the LTG concentrations considerably (by 54%). The inducing effect of OCBZ (29%) was less pronounced but also significant. The inducing effect of MSM, CBZ, and OCBZ was also seen in combination with VPA: VPA alone increases the LTG concentration approximately 211%, whereas in addition to MSM (8%), CBZ (21%), or OCBZ (111%), the increase of LTG was significantly smaller. The analysis of variance confirmed the results of the regression analysis. The effect of MSM on the LTG concentration should be considered if MSM is added or withdrawn in patients treated with LTG. Oxcarbazepine had a less pronounced inducing effect on LTG metabolism compared to CBZ. If CBZ is replaced by OCBZ as comedication, an increase in LTG serum concentrations should be expected.

Adolescent↗
PubMed1998

Comparison of total and free phenytoin serum concentrations measured by high-performance liquid chromatography and standard TDx assay: implications for the prediction of free phenytoin serum concentrations.

The free fraction of phenytoin (PHT) in serum increases considerably in combination with valproic acid (VPA), depending on the VPA concentration. Equations to predict the free PHT concentration (PHTf) from the total PHT concentration (PHTt) and from the VPA concentration were developed by Haidukewych and colleagues. (equation 1: PHTf = 0.095 x PHTt + 0.001 x VPA x PHTt) and May and colleagues (equation 2: PHTf = 0.0792 x PHTt + 0.000636 x VPA x PHTt]; in both equations, PHTf, PHTt, and VPA are given in microg/ml. Obviously, the equations give different predictions. The aim of this study was to investigate whether different methods for the determination of PHTt and PHTf were responsible for the differences; equation 1 was calculated from standard TDx measurements and equation 2 from high-performance liquid chromatography (HPLC) values. A total of 52 samples from patients with VPA (n=26) or without VPA (n=26) were analyzed using HPLC and TDx. The concentrations measured by HPLC and TDx were highly correlated but TDx yields significantly higher PHTt (Y = 0.98 x X + 2.46; X = HPLC, Y = TDx, r2 = 0.957) and, in particular, higher PHTf concentrations (Y = 1.03 x X + 0.30; X = HPLC, Y = TDx, r2 = 0.919), compared with our HPLC method. The accuracy of the predictive equations depends on the method used for the determination of PHTt and PHTf. The best predictions of PHTf were obtained if equation 2 and HPLC measurements were used. However, the differences in the predicted PHTf could only partly be explained by the different methods of determination.

Chromatography, High Pressure Liquid↗
PubMed1997

Cerebellar atrophy decreases the threshold of carbamazepine toxicity in patients with chronic focal epilepsy.

BACKGROUND: Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. Since gaze-evoked nystagmus, dizziness, and ataxia are some of the typical adverse effects (AEs) of the dose-dependent toxicity of carbamazepine, preexisting CA could possible explain in part the interindividual variation in the tolerance of high serum concentrations of carbamazepine. OBJECTIVE: To determine whether CA reduces the threshold for overdose symptoms with carbamazepine in patients with chronic focal epilepsy in a prospective study. DESIGN: Cohort study. SETTING: A fourth-level epilepsy center to which patients were referred. PATIENTS: Twenty-six consecutive patients with chronic focal epilepsy were prospectively studied while they were receiving high-dose monotherapy with carbamazepine. Patients were slowly titrated to doses at which the first toxic AEs of carbamazepine occurred. The determination of multiple serum levels was carried out, together with an evaluation of toxicity that comprised a standardized neurologic examination, a questionnaire for AEs, and posturography. MAIN OUTCOME MEASURES: Serum concentrations of carbamazepine at the occurrence of the first dose-dependent AEs were related to the presence or absence of CA in magnetic resonance imaging studies as rated by 2 independent and blinded neuroradiologists. RESULTS: In 9 patients (35%), magnetic resonance imaging scans revealed moderate (n = 7) or severe (n = 2) CA. In these patients, gaze-evoked nystagmus (P = .001, log rank test), dizziness (P = .008), and ataxia of stance as measured by posturography (P = .02) occurred at significantly lower serum concentrations of carbamazepine compared with patients without CA. This was also found for the first individually observed AE (P = .03). CONCLUSION: Cerebellar atrophy occurs in a considerable percentage of patients with chronic focal epilepsy and obviously increases the susceptibility for cerebellar AEs of carbamazepine.

Adolescent↗
PubMed1997

Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child.

OBJECTIVE: To investigate the transfer of lamotrigine in pregnancy and during lactation from a mother on lamotrigine treatment to her child. METHODS: Concentrations of lamotrigine were measured by high-pressure liquid chromatography in umbilical cord serum and in serum samples of the mother and her child as well as in the mother's milk during the first five postpartum months. RESULTS: In the child lamotrigine serum concentrations (up to 2.8 micrograms ml-1) comparable to those usually achieved in active treatment with lamotrigine were found not only after birth, but also during lactation. A considerable amount of lamotrigine (2-5 mg per day) was excreted in breast milk. No adverse effects were seen in the child. CONCLUSION: The transfer of lamotrigine taking place during pregnancy and lactation should not be neglected. In this case the child should be thoroughly observed for potential adverse effects.

Adult↗
PubMed1996

Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication.

Lamotrigine (LTG) is a new antiepileptic drug (AED), chemically unrelated to the drugs in current use. Previous studies have shown that LTG has only a limited effect on other AEDs, but its own metabolism can be strongly induced or inhibited by the comedication. We investigated the influences of carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproic acid (VPA), and combinations of these drugs on the serum concentration of LTG. A total of 588 blood samples from 302 patients were analyzed. The mean duration of LTG therapy was 141 +/- 137 days (mean +/- SD). A patient was only considered twice in this study if his or her comedication had been changed. The LTG serum concentration in relation to LTG dose/body weight (level-to-dose ratio, LDR, microgram/ml/mg/kg) was calculated and compared for different drug combinations. The results showed that comedication had a highly significant (p < 0.001) influence on the LTG serum concentrations. The mean LDR for LTG was 0.32 (LTG + PHT) < 0.52 (LTG + PB) approximately equal to 0.57 (LTG + CBZ) < 0.98 (LTG mono) approximately equal to 0.99 (LTG + VPA + PHT) < 1.67 (LTG + VPA + CBZ) approximately equal to 1.80 (LTG + VPA + PB) < 3.57 (LTG + VPA (<, p < 0.05; approximately equal to, p > 0.05, multiple comparisons). The mean LTG concentrations in patients on comedication with VPA were about two times higher than on patients on LTG monotherapy or on comedication without VPA (5.0 vs. 2.6 micrograms/ml), despite the LTG doses being half as high (3.0 vs. 5.9 mg/kg). The correlations of the serum concentrations and doses of CBZ, PB, PHT, and VPA with the LDR of LTG were only weak or not significant. Furthermore, the distribution of LTG serum concentrations and dosages was compared with the tentative therapeutic range for the LTG concentration (1-4 micrograms/ml), proposed by some investigators, and the recommendations for the LTG dosage. Remarkable discrepancies were observed. The comedication has an important influence on the LTG concentration and should be considered in LTG dosage.

Adult↗
PubMed1996

Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients.

Oxcarbazepine (OCBZ) is a new antiepileptic drug with a chemical structure similar to carbamazepine. We investigated the daily fluctuations of 10-OH-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of OCBZ, in patients with or without comedication. Twenty-two profiles of (total) serum concentrations of MHD from 18 epileptic patients on a b.i.d. OCBZ regimen were determined at 8.00, 11.00, 14.00, 17.00, 20.00 h (and 22.00 h/23.00 h). A patient was only considered twice if his comedication or OCBZ dosage had been changed. The maximal MHD concentrations were about 33% +/- 14% higher than the minimal MHD concentrations during the day. The free MHD concentrations were determined in 17 profiles. The mean free fraction of MHD was 56.7% +/- 5.5%. In combination with valproic acid the free fraction (64.0% +/- 1.4%) was slightly, but significantly higher (p < 0.05) than in monotherapy (52.3% +/- 0.9%) or in combination (58.0% +/- 2.6%) with other antiepileptic drugs (2 x phenobarbital, 2 x methsuximide, 1 x sulthiame). Further studies are necessary to clarify if the observed fluctuations of MHD are of clinical importance.

Adolescent↗
PubMed1995

Lack of effect of histological lesions on the phenytoin and phenobarbital concentrations in the brain cortex of epileptic patients.

Postmortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined in 24 specimens of the frontal, temporal, occipital or neocerebellar cortex with different pathological changes and in the serum (total and free) from 11 epileptic patients. The cortical lesions were characterized by various degrees of neuronal loss or necrosis associated with other changes such as proliferated gliocytes, fibre gliosis, Rosenthal fibres or numerous corpora amylacea. According to other investigators neurons are the main binding sites of PHT and PB in rodent brains. The PHT and PB concentrations in 20 cortical lesions from nine patients were not significantly reduced as compared to the data of 46 deceased epileptic control patients. A significantly decreased PB value could only be demonstrated in the temporal specimen of an old scarred infarction with complete demyelination. On the other hand a slight but significant increase of PB was observed in three neocortical samples from a child exhibiting severe brain oedema and thrombosis of the sinuses. The results favour the unspecific binding of PHT and PB to cerebral tissue constituents and do not support the hypothesis of major binding to specific receptors.

Aged↗