Search PubMed⌕ Search

Biomedical subjects

W J Adams

Publications and source records attributed to W J Adams.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans.

The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: 1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; 2) chiral inversion of R-(-)-[2H3]ibuprofen is not subject to a discernible deuterium isotope effect; and 3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence.

Adult↗
PubMed1986

Phase I study of intravenous menogaril administered intermittently.

Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic. The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2. The maximum tolerated dose was 250 mg/m2. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks. There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2. Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement. Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients). Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days. Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed. Nausea and vomiting were uncommon and never severe. Alopecia and mucositis were rare. Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop. Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2. Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.

Adult↗
PubMed1985

Calculated T1 images derived from a partial saturation-inversion recovery pulse sequence with adiabatic fast passage.

Calculated T1 images of the head and abdomen have been obtained using an alternating partial saturation-inversion recovery pulse sequence. Timing parameters were adjusted to yield optimum T1 contrast-to-noise ratio for this sequence for the range of T1 studied. Adiabatic fast passage (AFP) was implemented for the nonselective inverting pulse, to reduce the sensitivity of the measurement to RF and static field inhomogeneity. A nonlinear frequency sweep was used to improve the efficiency of the AFP pulse. The effect on the T1 calculation of slice selection during the pi/2 pulses was also determined and corrected for in the image reconstruction algorithm. The T1's determined by this method show a standard deviation of less than 10%, and good agreement with the literature.

Abdomen↗
PubMed1985

Selective time-reversal pulses for NMR imaging.

Using a nonlinear systems approach, a selective time-reversal pulse for multiple-slice-multiple-echo NMR imaging sequences has been developed. The results of both computer simulation and experiments on a 1.5 T imaging system demonstrate the markedly improved selectivity of the pulse compared to conventional time-reversal pulses.

Computers↗
PubMed1985

The missing triad: the case of two-child families.

Families, as they grow, become more complex in their psychosocial development. They also become more complex in their dyadic/triadic structure through the simple addition of another child. This article traces some of the structural changes that families undergo with the entry of each new child. It also raises several questions about how these very structures may, in turn, influence development of the children. By comparing two- and three-children families with different dyadic/triadic structures, these questions offer some basis for possible future research, as well as some speculation for the clinician.

Decision Making↗
PubMed1983

Absorption of triazolam from pelleted drug-diet mixtures by the mouse: quantitation of alpha-hydroxytriazolam in urine.

The absorption of triazolam from pelleted drug-diet mixtures by mice under steady-state conditions was determined for doses up to 150 mg/kg/day by measuring alpha-hydroxytriazolam, the principal urinary metabolite of triazolam in the mouse, in urine samples collected over a 24-hour period. Following beta-glucuronide glucuronosohydrolase hydrolysis of the urine, quantitation of alpha-hydroxytriazolam was accomplished using a specific reverse-phase liquid chromatographic method which utilized UV detection at 214 nm. Assay precision was greater than 2.7% (CV) over the concentration range of interest. Statistical analysis of the excretion data indicated that the mathematical relationship between the triazolam dose and the quantity of alpha-hydroxytriazolam excreted was linear for female mice and nonlinear for male mice. Triazolam absorption, as reflected by alpha-hydroxytriazolam urinary excretion data, increased with triazolam dose.

Animals↗
PubMed1979

Specific and sensitive high-performance liquid chromatographic determination of glyburide.

A specific and sensitive high-performance liquid chromatographic method has been developed for the rapid determination of intact glyburide in dog serum. With butylparaben as an internal standard, 1 ml of acid-buffered serum was extracted with toluene and an aliquot of the toluene was evaporated to dryness. The redissolved residue was chromatographed on a microparticulate reversed-phase column, and quantitation was achieved by monitoring the UV absorbance of the eluate at 228 nm. The response was linear, and the lower detection limit was approximately 20 ng/ml. Assay precision, as estimated by analyzing replicate samples of a laboratory standard, was better than 6% (CV). The utility of the analytical methodology for the determination of this highly potent sulfonylurea in pharmacokinetic studies in the dog was demonstrated.

Animals↗