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Biomedical subjects

T W May

Publications and source records attributed to T W May.

35 records · Page 2Linked to original sources
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↗
PubMed1994

Pharmacokinetics of sulthiame in epileptic patients.

Sulthiame is an antiepileptic drug that was introduced approximately 30 years ago for the treatment of epilepsy. Currently it is rarely used, but recent studies show its efficacy, especially in the treatment of focal epilepsies in children. Because there are hardly any pharmacokinetic studies of sulthiame in humans, we studied the dose-level relationship, the elimination half-life, and the daily fluctuations in the concentration of sulthiame among children and adults with epilepsy. The evaluation of the sulthiame serum concentrations of 86 patients gave, considering age and comedication, a relatively high correlation (r = 0.82) between the sulthiame dose/body weight and the sulthiame serum concentration. Children on a comparable sulthiame dose per body weight have lower sulthiame concentrations than adults. In our study sulthiame was, with few exceptions, administered in combination with other antiepileptic drugs. The sulthiame serum concentrations were lower in comedication with carbamazepine than with valproic acid. The evaluation of the individual sulthiame dose-level relationship of 8 patients showed in most cases a close and linear relationship. After withdrawal of sulthiame in 11 patients, short elimination half-lives (8.65 +/- 3.10 h) were estimated. This was in accordance with the large daily fluctuations in the sulthiame concentrations (swing: 103.9 +/- 59.3%) of the nine patients examined. The shorter half-lives and higher daily fluctuations in children indicate a higher clearance of sulthiame among children.

Adolescent↗
PubMed1994

Comparison of phenytoin and carbamazepine serum concentrations measured by high-performance liquid chromatography, the standard TDx assay, the enzyme multiplied immunoassay technique, and a new patient-side immunoassay cartridge system.

Steady-state concentrations of phenytoin (PHT) and carbamazepine (CBZ) were measured by a novel patient-side immunoassay system with a single-use cartridge (Biotrack 516). The Biotrack determinations were performed in whole blood and extrapolated to serum on the basis of the hemoglobin content. The results were compared with serum concentrations measured by high-performance liquid chromatography (HPLC) or the standard TDx and enzyme multiplied immunoassay (EMIT) techniques. A total of 222 samples from epileptic patients on PHT and 322 samples from patients on CBZ were analyzed. In the case of PHT there was a highly linear correlation [r = 0.985, y = 1.113x-0.589; x = HPLC, y = Biotrack] between HPLC and the Biotrack system in the concentration range of 2.5-30 micrograms/ml. In the case of CBZ, the correlation between HPLC and the Biotrack system in the concentration range of 2.0-20 micrograms/ml was somewhat lower [r = 0.931, y = 1.29x-0.136; x = HPLC, y = Biotrack]. Comparable results were also found for the correlation of the Biotrack system with the TDx assay or with the EMIT assay, respectively. Comedication had no influence, or only a minor influence (valproic acid), on the concentration of PHT and CBZ measured by the Biotrack system. Furthermore, the concentration of the metabolite carbamazepine-10, 11-epoxide had no influence on the concentration of CBZ measured by the Biotrack system. Since the automated cartridge system is simple, can be used rapidly, and is performed with only a few drops of blood, this technique offers some advantages for routine clinical use, especially under outpatient conditions.

Carbamazepine↗
PubMed1994

Concentrations of carbamazepine and carbamazepine-10, 11-epoxide in serum, brain tumors and paratumorous cortex: a prospective study of 37 neurosurgically treated epileptic patients.

Concentrations of carbamazepine (CBZ) and its metabolite carbamazepine-10, 11-epoxide (CE) were determined in serum (free and total), brain tumors and paratumorous cortex from 37 epileptic patients. Tumor biopsies were available from 25 different gliomas, 5 hamartomas and 1 angioma. The free serum concentrations of CBZ and CE were highly correlated with the corresponding paratumorous concentrations (r = 0.94 and r = 0.93) and to a lower extent with the tumorous concentrations (r = 0.78 and r = 0.75). For CBZ the concentration ratios paratumorous cortex/serum free and tumor/serum free showed no significant differences between CBZ-resistant and -nonresistant patients. Apart from histological grade a significant influence of type and site of the tumors on their CBZ and CE concentration was not recognizable. The results indicate that resistance to CBZ therapy cannot be sufficiently explained by decreased paratumorous or tumorous levels of CBZ and CE.

Adolescent↗
PubMed1992

Effects of withdrawal of phenytoin on cognitive and psychomotor functions in hospitalized epileptic patients on polytherapy.

The effects of the withdrawal of phenytoin (PT) on cognitive and psychomotor functions of long-term patients in an epilepsy centre were studied. The patients had been treated for many years (31.1 +/- 10.8 yrs.) with PT in combination with other antiepileptic drugs. The serum concentration of PT was in the lower to middle therapeutic range (6.8 +/- 3.1 mg/l). Only patients in which the efficacy of PT was questionable were included in the study. PT was withdrawn in 17 patients. The PT dose was not changed in 12 patients (control group). Psychological tests were carried out immediately before the withdrawal of PT and about 10 weeks later. Tests were also carried out with the control group at the same time. A significantly improved performance (using a composite score) was noted after the withdrawal of PT. The statistical evaluation of the different tests showed an significant improvement in one test of concentration and two tests of psychomotor function (tapping and pursuit rotor with the dominant hand). There was no significant change in the frequency of seizures.

Adult↗
PubMed1991

Nomogram for the prediction of unbound phenytoin concentrations in patients on a combined treatment of phenytoin and valproic acid.

The interpretation of the total phenytoin (PT) concentration can be problematic if valproic acid (VPA) is given as a comedication, because VPA displaces PT from the protein binding sites and can increase the free fraction of PT. In order to estimate the free or unbound PT concentration (PTf) from the total PT concentration (PTt) and VPA concentration, a nomogram was constructed and evaluated. Data of 84 patients on combined therapy with PT and VPA were used in drawing up the regression equation (PTf = 0.0792.PTt + 0.000636.PTt.VPA) from which the nomogram was constructed. The predictions were checked using another 33 patients whose serum concentrations were determined in the morning and in addition several times during the day. The results show that using this method the PTf concentrations can be accurately estimated from the PTt and VPA concentrations.

Adolescent↗
PubMed1988

Trace element residues in bluegills and common carp from the lower San Joaquin River, California, and its tributaries.

Whole-body samples of bluegills (Lepomis macrochirus) and common carp (Cyprinus carpio) from the San Joaquin River and two tributaries (Merced River and Salt Slough) were analyzed to determine if the concentrations of any of nine elements were elevated as a result of exposure of the fish to agricultural subsurface (tile) drainage water. Highest concentrations (micrograms/g dry weight) detected were as follows (first number in each pair applies to bluegills and the second to carp): arsenic (As), 0.97 and 1.5; boron (B), 14 and 20; cadmium (Cd), 0.14 and 0.27; chromium (Cr), 2.7 and 2.2; mercury (Hg), 3.3 and 2.9; molybdenum (Mo), 2.8 and 3.6; nickel (Ni), 0.87 and 2.2; lead (Pb), 0.26 and 2.3; and selenium (Se), 3.2 and 5.5. The lowest concentrations were below the levels of detection, except for Hg (0.15 in bluegills and 0.12 in carp) and Se (0.43 and 0.56). As judged by comparisons with data from the National Contaminant Biomonitoring Program and other published surveys, the concentrations of B, Hg, Mo, and Se were moderately elevated in fish from several sites in the San Joaquin Valley. However, only the Se concentrations were positively correlated with water quality variables (e.g., total alkalinity, conductivity, and turbidity) known to be influenced by irrigation return flows. Historical data from one site (Salt Slough), where trace elements in whole fish have been measured since 1969, indicated that Se concentrations increased more than twofold between 1973 and 1977, but thereafter remained near 3.0 micrograms g-1 (dry weight basis), presumably due to the continuing practice of disposing seleniferous tile drainage water into the most convenient stream channel.

Animals↗
PubMed1982

Recovery of endogenous selenium from fish tissues by open system dry ashing.

Quantitative recovery of endogenous selenium from fish tissues following dry ashing techniques has not been confirmed. An open system dry ashing procedure, using oxidative fusion with Mg(NO3)2 X 6H2O in the presence of MgO, was tested for recovery of selenium from National Bureau of Standards (NBS) Reference Materials (tuna and oyster) and selected fish tissues. Recovery after dry ashing and hydride analysis was complete from NBS Bovine Liver, Tuna, and Oyster Tissues, as well as from Food and Drug Administration cod, haddock, perch, and flounder research materials. Endogenous selenium, injected into rainbow trout (Salmo gairdneri) as 75Se, was recovered after ashing from liver, ovaries, gastrointestinal tract, muscle, bile, and carcass, 3 and 10 days post-injection. Results indicate that open vessel oxidative fusion is a rapid, simple technique applicable to quantitative recovery of selenium from organoselenium compounds that exist in various aquatic species. The diluted digestate is readily amenable to conventional hydride generation analysis.

Animals↗
PubMed1981

Cadmium, lead, mercury, arsenic, and selenium concentrations in freshwater fish, 1976-77--National Pesticide Monitoring Program.

As part of the National Pesticide Monitoring Program, the Fish and Wildlife Service, U.S. Department of the Interior, collected freshwater fish during 1976--77 from 98 monitoring stations and analyzed them for residues of cadmium, lead, mercury, arsenic, and selenium. Range and geometric mean values in mg/kg wet weight follow: Cd, 0.01--1.04, 0.07; Pb, 0.10--4.92, 0.32; Hg, 0.01--0.84, 0.11; As. 0.05--2.92, 0.27; Se, 0.05--2.87, 0.56. An arbitrary 85th percentile was calculated for concentrations of each element in fish to identify monitoring stations having fish with higher-than-normal concentrations: Cd, 0.11 mg/kg; Pb, 0.44; Hg, 0.19: As, 0.38; Se, 0.82. Log-transformed mean concentrations in fish from 1976--77 monitoring stations are compared with means from the same stations in 1972 (Cd, Hg, Pb, As, Se) and 1973 (Se) to depict temporal trends in whole-body concentrations: Cd, significant decline; Pb, no significant difference; Hg, significant decline; As, significant increase; Se, no significant difference. Because of changes in laboratories and analytical procedures, these conclusions should be used cautiously as trend information. Production, consumption, and disposal of cadmium, lead, mercury, arsenic, and selenium are discussed as potential environmental sources of the elements to the aquatic environment. Specific environmental sources are suggested for monitoring stations having trace element levels exceeding calculated 85th percentiles.

Animals↗
PubMedDate not supplied

Residues of organochlorine insecticides, polychlorinated biphenyls, and heavy metals in biota from Apalachicola River, Florida, 1978.

Seventy-seven composite samples composed of largemouth bass ( Micropterus salmoides ), channel catfish ( Ictaluras punctatus), threadfin shad ( Dorosoma petenense ), Asiatic clam (Corbicula fluminea ), burrowing mayfly ( Hexagenia sp.), water snake ( Natrix spp.), and little green heron ( Butorides virescens ) were collected from upper and lower reaches of the Apalachicola River, Florida, in 1978 for residue analysis of organochlorine insecticides, PCBs (polychlorinated biphenyls), and metals. Compared with data from the National Pesticide Monitoring Program and criteria recommended for the protection of aquatic life, residue concentrations were moderately high in the Apalachicola River. Biota from the upper river generally had higher organic and lower metal residues than those from the lower river. Highest residues in the biota were total DDT, total PCBs, and toxaphene. Although individual mean concentrations were below 2 micrograms/g and total organic contaminant residues never exceeded 5 micrograms/g, residue concentrations of DDT, PCBs, and toxaphene (particularly from the upper river) exceeded recommended permissible levels for the protection of aquatic life. Metal residues were generally below 1 microgram/g. Exceptions were arsenic residues in threadfin shad (1.07 micrograms/g) and Asiatic clams (1.75 micrograms/g), and selenium in eggs of channel catfish (1.39 micrograms/g). The residues observed in the biota, particularly from the upper station, indicated moderate contamination of the Apalachicola River system at the time samples were collected.

Animals↗
PubMedDate not supplied

Evaluation of cryogenic impact grinding technique for powdering whole fish for metal determinations.

A cryogenic grinding technique, which involves brittle fracture of samples by impact pressure, was evaluated for the final reduction of whole-fish samples for subsequent metal determinations. The technique incorporated a number of desirable features: protection of heat-labile components; incorporation of lyophilization to facilitate handling and storage; requirement of few procedural steps; short grinding time per sample; and easy, rapid cleanup of equipment. Particle size in the ground powder was less than 100 microns. Problems associated with the technique were contamination of fish samples with Cr, Fe, Mo, and Ni; limited size of the grinding container; and powder clumping caused by the presence of lipids. Approaches to alleviate these problems are discussed.

Animals↗