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Biomedical subjects

A A Miller

Publications and source records attributed to A A Miller.

At least 73 records · Page 4Linked to original sources
PubMed1985

Changes in cortical amino acids during electrical kindling in rats.

The effect of kindling rats by electrical stimulation of the frontal cortex for approx. 3 months on the concentrations of amino acids (taurine, aspartate, glutamate, glutamine and GABA) in the cerebral cortex has been studied, as well as the release of endogenous amino acids from kindled slices of brain in vitro. In these kindled rats, killed 1 week after the last shock, there were no changes in any concentrations of amino acids. However, when cortical slices, prepared from either the control or kindled rats, were stimulated in vitro by exposure to veratrine, more endogenous glutamate and aspartate were released from the kindled tissue than from the control. The neurotransmitter amino acids, glutamate and aspartate, may be involved in the permanent effects of electrical kindling.

Amino Acids↗
PubMed1985

Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam.

Twelve healthy male volunteers received phenytoin 0.5 and 1 g, lamotrigine (a new anticonvulsant) 120 and 240 mg, diazepam 10 mg and placebo orally in a double-blind, cross-over, randomized trial. Maximum drug concentrations at 4 h, measured in plasma were 11.5 +/- 2.2 micrograms ml-1 for phenytoin and 2.7 +/- 0.4 micrograms ml-1 for lamotrigine. These levels were in the therapeutic range for phenytoin and the putative therapeutic range for lamotrigine. Side effects after diazepam (mainly sedation) and phenytoin (mainly unsteadiness) differed markedly from lamotrigine which produced no important side effects. Subjective effects as measured by visual analogue scales were caused by phenytoin and diazepam but not by lamotrigine. Diazepam impaired eye movements, adaptive tracking and body sway. Phenytoin impaired adaptive tracking, increased body sway and impaired smooth pursuit eye movement. Lamotrigine produced only a possible slight increase in body sway. There were significant correlations between performance and saliva levels of phenytoin and diazepam. It was concluded that the tests used were suitable for monitoring CNS effects of anticonvulsants and that lamotrigine possibly could have a more favourable CNS side effect profile than phenytoin.

Adult↗
PubMed1985

[High-dose cytarabine treatment in acute leukemias and leukemic meningiosis: clinical aspects and pharmacokinetics].

Clinical reports concerning the therapeutic effects of high dose Cytosine arabinoside (HD Ara-C) in meningeal leukemia are relatively rare. Pharmacokinetic studies, however, have indicated potentially effective concentrations of Ara-C in cerebrospinal fluid (CSF) during and after high-dose infusions of the drug given intravenously. In this report, the treatment results of HD Ara-C in 14 patients with refractory or relapsed acute leukemia are presented including those of 2 patients with meningeal leukemia. In these 2 patients as well as in 1 patient without central nervous system (CNS) leukemia, Ara-C and Ara-U concentrations in CSF and plasma were measured during a 6-day therapy with HD Ara-C (3 g/m2 q 12h 12 X). Ara-C and Ara-U levels were determined on Days 3 and 6 of therapy, each at the end of a 3-h i.v. infusion of the drug. In the 14 patients (8 with AML, 6 with ALL) treated, a total number of 17 treatment cycles were given for remission induction with doses of Ara-C ranging from 1-3 g/m2 q 12 h 6-12 X. A complete remission rate of 47% was achieved. The duration of remission ranged from 1 to 6 months. Of the 2 patients with CNS leukemia, 1 patient achieved complete remission both in CSF and in bone marrow, the other patient only in CSF. The mean concentration of Ara-C in CSF was 903 ng/ml with a ratio of 0.38 to that in plasma. Ara-C and Ara-U did not appear to accumulate in CSF or in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1983

Reduced cortical glutamine concentrations in electrically kindled rats.

The effect of kindling rats (with an electrical stimulus applied daily to the frontal cortex) on the concentrations of taurine, aspartate, glutamate, glutamine, and gamma-aminobutyric acid has been investigated. When compared with control groups, cortical glutamine concentrations were significantly decreased in kindled rats by approximately 20%. This decrease in glutamine directly correlated with the after-discharge duration (r = 0.84, p = 0.005). The significance of this in relation to glutamate metabolism and kindling is discussed here.

Amino Acids↗
PubMed1983

Pharmacological and biochemical interactions of N-(phosphonacetyl)-L-aspartate and 5-fluorouracil in beagles.

N-(Phosphonacetyl)-L-aspartate (PALA) and 5-fluorouracil (FUra) are both antimetabolites that affect the biosynthetic pathways of pyrimidines. To determine whether these two drugs exhibit synergistic pharmacological or biochemical interactions, we determined the pharmacological and biochemical parameters of PALA and [14C]FUra in 14 beagle dogs which received i.v. bolus administrations of either the single agents or the drug combination. The pharmacokinetic parameters of PALA (four dogs, 20 mg/kg) in plasma, cerebrospinal fluid, and urine were not changed by FUra (10 mg/kg, 30 min after PALA). The pharmacokinetics of [2-(14)C]FUra (six dogs, 10 mg/kg, 20 muCi/kg) was characterized by higher FUra plasma concentrations after pretreatment with PALA (20 mg/kg, 30 min before FUra); this led to a significantly larger area under the drug concentration-time curve, a decreased volume of distribution, and a reduced clearance rate and was associated with higher cerebrospinal fluid concentrations of FUra. The FUra plasma and cerebrospinal fluid half-lives, however, were not significantly altered by PALA. The biochemical determinants of PALA and FUra activity were studied in intestinal mucosa, liver, thymus, spleen, and bone marrow of four dogs. Although the activity of the target enzyme of PALA, L-aspartate carbamoyltransferase, in tissue extracts was decreased at least 50% at 18 to 24 hr after PALA administration (50 mg/kg), the uridine nucleotide pools remained remarkably stable. Intracellular FUra concentrations were not influenced by PALA. The incorporation of 5-fluorouridine triphosphate into RNA was enhanced in intestinal mucosa and liver. In other tissues, however, fluorouridine nucleotide concentrations were not affected by PALA. Free 5-fluorodeoxyuridine monophosphate had the highest concentration in liver and was detectable in all tissues, but it was not altered by PALA treatment. Our results show that the pharmacological and biochemical events after FUra exposure are marginally modulated by PALA in normal dogs. If sensitive tumors with a higher degree of interaction between the two drugs could be identified, limited toxicity to normal tissues can be expected.

Animals↗
PubMed1983

Negative-ion chemical-ionization mass spectrometry of aclarubicin analogs and characterization of two metabolites in man.

Aclarubicin and seven analogs have been characterized by negative-ion chemical-ionization mass spectrometry. The method is highly sensitive (requires 1-10 ng) because of the stable semiquinone radical anions that are produced by resonance electron capture of thermal electrons. Ions in the spectra correspond to the intact molecule (M), M-H2O, aglycone, aglycone-O, and aglycone-2H2O. In addition, ions corresponding to the sequential loss of carbohydrate groups are exhibited in the spectra of compounds with di- and tri-saccharides. Two aclarubicin analogs were isolated from a patient's plasma and were found to be bisanhydroaklavinone, F, and one or both of the epimeric reduction products of the L-cinerulose carbonyl, M1 and N1.

Aclarubicin↗
PubMed1982

Comparison of the reversed-phase high-performance liquid chromatographic separations of fluoropyrimides, pyrimidines, and purines.

The reversed-phase, high-performance liquid chromatographic separation of fluoropyrimidines, pyrimidines, and purines was investigated under isocratic conditions at ambient temperature. The performance of nine analytical, commercially available columns with five mobile phases is compared, and capacity and resolution factors are reported. The variables determining resolution are discussed, and the systems accomplishing the desired separation of fluoropyrimidine and pyrimidine bases and nucleosides are described. The best chromatographic results are achieved by using Spherisorb ODS-2 as stationary phase and 0.05 M monobasic ammonium phosphate (pH 3.5) as mobile phase.

Chromatography, High Pressure Liquid↗
PubMed1979

Features of trisomy 18 and 18p- syndromes in an infant with 45,XY,i(18q).

An isochromosome for the long arm of chromosome number 18 - 46,XY,i(18q) - was found in an infant who had features of both trisomy 18 and 18p- syndromes. Findings compatible with trisomy 18 included postmature delivery, prominent occiput, severe congenital heart disease, overlapping fingers, and rocker-bottom feet. Those of 18p- syndrome, which frequently resembles Turner syndrome, were downward obliquity to the palpebral fissures, short, webbed neck, low posterior hairline, and widely-spaced nipples. The infant died of heart failure at 3.5 months of age. Parental karyotypes were normal.

Abnormalities, Multiple↗
PubMed1978

Legionnaires' disease in Vermont, May to October 1977.

Thirty-two confirmed and 24 highly probable cases of Legionnaires' disease occurred in Vermont between May 1 and Oct 15, 1977. Confirmed cases had positive results for direct fluorescent antibody testing of lung tissue or fourfold rise in antibody titer. Highly probable cases had one elevated titer (greater than or equal to 1:256) and a compatible illness. Forty-eight (86%) had underlying chronic disease, and 22 (39%) were immunocompromised. Prominent early symptoms were fever, cough, chills, and malaise. All but one patient had verified pneumonia. Courses ranged from a pneumonia not requiring hospitalization to respiratory failure necessitating support with mechanical ventilation. Seventeen patients died. Although the clinical presentation was variable, rapid development of high fever and leukocytosis together with negative cultures of lower respiratory tract secretions strongly suggested the diagnosis in an epidemic setting.

Adult↗