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Biomedical subjects

C P Turley

Publications and source records attributed to C P Turley.

17 recordsLinked to original sources
PubMed1993

Alpha-tocopherol protects against a reduction in adenosylcobalamin in oxidatively stressed human cells.

Excretion of methylmalonic acid by vitamin E-deficient patients and decreased labeling of adenosylcobalamin (AdoCbl) from cyanocobalamin in vitamin E-deficient rats suggest an interaction of vitamins E and B-12. We studied this interaction in two human cell culture systems: foreskin fibroblasts and a hepatoma cell line (HepG2). We measured radiolabeling of AdoCbl and methylcobalamin from [57Co]hydroxycobalamin for 6 d in the presence and absence of linoleate (an oxidative stressor) and alpha-tocopherol. In both cell types, labeling of AdoCbl was lower in the presence of linoleate unless alpha-tocopherol was present. The decrease was accentuated by peroxidized linoleic acid; AdoCbl synthetic rate was inversely associated with thiobarbituric acid-reactive compound concentration. Subcellular partitioning of labeled cobalamin revealed less in mitochondria in the linoleate-stressed cells that were not treated with alpha-tocopherol. We conclude that lipoperoxidation reduces mitochondrial AdoCbl formation and that alpha-tocopherol exerts a protective effect in oxidatively stressed cells. We suggest that this subcellular deficiency in AdoCbl may be one mechanism by which vitamin E deficiency leads to neurologic injury. The mechanism seems primarily to involve an alteration in intracellular cobalamin distribution with perhaps a minor effect upon enzymes of AdoCbl synthesis.

Carcinoma, Hepatocellular↗
PubMed1990

Phenytoin protein binding in pediatric patients with acute traumatic injury.

Phenytoin (DPH) is commonly used to treat seizures associated with acute head injury. Consequent to decreases in DPH protein binding in such patients, the DPH free fraction (DPHff) may increase and thereby produce symptoms compatible with DPH toxicity despite the presence of total serum concentrations within the usually accepted therapeutic range. We examined the effect of acute traumatic injury on DPH protein binding in 13 hospitalized pediatric patients. In addition to total and free DPH serum concentrations, biochemical variables including blood pH, total and direct bilirubin, serum urea nitrogen, creatinine, albumin, gamma glutamyltransferase (GGT), and free fatty acid concentrations were measured serially over 10 days. The DPHff was compared between selected time intervals in hospitalized patients and data obtained in a control population of 27 epileptic outpatients who were maintained on DPH. Additionally, a multiple regression model was used to examine for covariance between the DPHff and the respective biochemical variables in the hospitalized patients. In the study patients, the DPHff progressively increased, attaining a maximum value (8.5 +/- 0.7%) on the fifth hospital day which was significantly greater (6.4 +/- 0.7%, p less than .05) than that on day 1 and also in the control group (6.1 +/- 0.3%; p less than .01). Blood pH, serum albumin, free fatty acids, creatinine and bilirubin concentrations did not change, but GGT did increase significantly over the 10-day sampling period. A significant (r = .51, p less than .0001) linear relationship was found between the DPHff and the serum albumin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

The use of serum electrolyte concentrations determined by automated analyzers to indirectly quantitate serum bromide concentration.

Bromide is not often prescribed today as antiepileptic therapy. One reason is that serum bromide concentrations are not routinely performed in hospital laboratories, making clinical decisions difficult. Because of bromide ion interference with the electrodes of commonly used automated electrolyte analyzers, factitious "hyperchloremia" (and in some cases, "hyperbicarbonatemia"), are produced. These values, and the resulting calculated anion gap, correlate well with the measured serum bromide concentration. The correlation permits results from routine automated electrolyte analyzers to be used to indirectly determine serum bromide concentration.

Acid-Base Equilibrium↗
PubMed1989

Pentobarbital quantitation using immunoassays in Reye's syndrome patient serum.

Analysis of serum pentobarbital concentrations in 28 specimens from Reye's syndrome patients was conducted with modifications of three nonspecific immunoassay procedures originally designed to detect barbiturates in serum or urine. An adaptation of the urine enzyme-multiplied immunoassay technique (EMIT) Dupont aca barbiturate screen to the quantitation of serum pentobarbital is described. Replicate analysis of control specimens containing pentobarbital across a wide spectrum of concentrations revealed a between-day precision of less than 6%. Regression analysis revealed excellent agreement with a high-performance liquid chromatography (HPLC) method: (HPLC) = 0.98 (aca) - 0.07 (r = 0.97). Multiple linear regression analysis with a serum EMIT barbiturate screen and a urine fluorescence polarization immunoassay screen modified to quantitate pentobarbital in serum revealed excellent agreement among all methods, demonstrating that immunoassays offer a reliable approach to pentobarbital quantitation.

Humans↗
PubMed1988

Microanalytical high-performance liquid chromatography assay for cefpirome (HR 810) in serum.

We report a microanalytical high-performance liquid chromatography method for quantitation of cefpirome (HR 810) from serum. The drug was extracted from 0.05 ml of serum with 0.2 ml of isopropanol containing beta-hydroxypropyltheophylline, the internal standard. Separations were performed on a C18 column at ambient temperature with detection at 240 nm. The mobile phase consisted of acetate buffer (0.05 M sodium acetate) containing tetrabutylammonium hydroxide and methanol (pH 5.1; 70:30, vol/vol). The method was linear to 500 micrograms of cefpirome per ml and had a sensitivity of 0.6 micrograms/ml. Analytical recovery was greater than 86%, and the between-day coefficient of variation was less than 4.2%. The stability for 1 week at 4 to 8 degrees C and for 30 days at -20 degrees C was documented. Interference with commonly used antibiotics, analgesics, methylxanthines, and anticonvulsants was not found. The small sample volume and ease of preparation make this method suitable for use in pediatric pharmacokinetic investigations of cefpirome.

Cephalosporins↗
PubMed1988

Protein binding of phenytoin and lidocaine in pediatric patients with type I diabetes mellitus.

We evaluated serum protein binding of phenytoin and lidocaine, the extent of albumin and hemoglobin glycation, and alpha-1-acid glycoprotein concentrations in 47 children and adolescents (9-17 years) with type I diabetes mellitus (DM). Serum was incubated with phenytoin (n = 47) and lidocaine (n = 32) to yield total concentrations of 19.4 +/- 1.34 and 4.6 +/- 0.5 mg/l, respectively. A serum ultrafiltrate was prepared from an aliquot of each sample by membrane centrifugation. Total and free concentrations of phenytoin (free fraction 8.3 +/- 1.0%) and lidocaine (free fraction 25.8 +/- 11.6%) were determined using a fluorescence polarization immunoassay technique. A linear relationship (r = 0.63, p = 0.0001, y = 40.1 + [-0.2x]) was also found between the alpha-1-acid glycoprotein concentration (68.5 +/- 20.9 mg%, range 47.2-134.7 mg%) and lidocaine-free fraction (n = 32). No relationship existed between the extent of glycated albumin and the lidocaine-free fraction, in contrast to the linear correlation (r = 0.49, p = 0.0005, y = 3.7 + 0.4x) found between the extent of glycated albumin and the free fraction of phenytoin in serum (n = 47). A similar correlation (r = 0.49, p = 0.014, y = 3.7 + 0.3x) was found between glycated albumin (%) and the phenytoin-free fraction (3.9 +/- 0.9%) when examined in a separate (n = 17) set of patient samples spiked to contain a total serum phenytoin concentration of 32.6 +/- 1.4 (range 29.4-35.7) mg/l. Our data demonstrate a predictable increase in the free fraction of phenytoin as the extent of albumin glycation increases in pediatric patients with type I DM who are in poor glycemic control. This relationship was not found for lidocaine, a representative basic compound. These findings suggest that glycation of albumin alters the binding of phenytoin in children and adolescents with type I DM.

Adolescent↗
PubMed1987

Alteration of phenytoin binding by glycosylation of albumin in IDDM.

We measured glycosylated albumin and hemoglobin and serum protein binding of phenytoin in 57 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Serum was incubated with phenytoin to yield concentrations of 15 and 25 mg/L, and a serum ultrafiltrate was prepared from an aliquot of each sample. We observed a linear correlation between glycosylated albumin and the free fraction of phenytoin at serum phenytoin concentrations of 15 mg/L (r = .35, P = .03) and 25 mg/L (r = .40, P = .003). A better correlation existed between the free fraction of phenytoin and total albumin concentrations for both serum concentrations (r = .45, P = .005 for 15 mg/L; r = .56, P = 10-5) for 25 mg/L), whereas the best linear correlation resided between the free fraction of phenytoin and the concentration of nonglycosylated albumin (r = .54, P = .0005 for 15 mg/L; r = .63, P less than 10(-6) for 25 mg/L). There was no correlation between the free fraction of phenytoin and the concentration of glycosylated albumin. Incubation of solutions of glycosylated and nonglycosylated albumin demonstrated significantly lower binding to the glycosylated fraction (P = 8.1 X 10(-6)). These results indicate that glycosylation of albumin diminishes the affinity of the phenytoin binding site on albumin. This alteration may have clinical significance in that it may alter the disposition of phenytoin in patients with IDDM and produce free phenytoin serum concentrations that are not accurately reflected by total serum phenytoin concentrations.

Adolescent↗
PubMed1986

The neurotoxicity of cyclotrimethylenetrinitramine (RDX) in a child: a clinical and pharmacokinetic evaluation.

Cyclotrimethylenetrinitramine (RDX) is a highly explosive compound frequently used for both military and civilian purposes. Previously reported cases of human RDX intoxication were limited to wartime settings and have described no human pharmacokinetic data. We report the first human intoxication to occur in a non-wartime setting. This intoxication presented with status epilepticus in a child and permitted the description of RDX human pharmacokinetics. It also suggested a strong association between central nervous system dysfunction and RDX intoxication.

Child, Preschool↗
PubMed1985

Rapid protein determinations on ultrafiltrates prepared for free phenytoin quantification.

Ultrafiltration techniques for the separation of bound and free ligand are dependent on minimal amounts of protein-bound drug leakage through the membrane devices. A dye-impregnated test strip protein assay (Chemstrip-9) provides a rapid, visual assessment of membrane protein leakage. The test strips are sensitive to 200 mg/L of albumin in ultrafiltrates and do not react with as much as 4 mg/L of phenytoin.

Blood Proteins↗