Rape and subsequent seroconversion to HIV.
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Biomedical subjects
Publications and source records attributed to R Hillman.
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We describe an immunoassay system suited to patient-side assay of therapeutic drugs and blood proteins. The system consists of an electronic monitor and single-use plastic cartridges containing dry reagents and liquid diluents. The monitor is turned on by insertion of a cartridge. To run the test, the user applies an unmeasured drop of blood to the cartridge when prompted by the monitor. All subsequent steps are performed without further user intervention and results are provided in less than 3 min. The system hemolyzes and precisely dilutes the blood. Hemoglobin concentration is measured, then the diluted blood is precisely diluted further and mixed with two dry reagents. The drug concentration is measured by a turbidimetric latex agglutination inhibition reaction. Theophylline and hemoglobin assay results for clinical samples correlate well with results of widely used comparison methods.
A microcomputer program for individualized drug level prediction based on Bayesian forecasting is presented. It is written so that the clinician can integrate patient demographics and drug levels to design a new dosage regimen tailored to an individual patient. The program's great flexibility and robustness make it appropriate for realistic clinical settings. A validation with a data set of lidocaine concentrations measured in 18 patients revealed that the program can predict serum lidocaine levels accurately enough to enhance individual patient dosage adjustment within a few hours after a dosage regimen is started.
We measured the biochemical response for four patients with maple syrup disease to pharmacologic doses of thiamine, and correlated their response to their branched chain alpha-ketoacid dehydrogenase activity. We observed a linear correlation between the concentrations of each plasma branched-chain amino acid and its corresponding ketoacid analogue. In addition, the renal tubular reabsorption of branched-chain amino and ketoacids was nearly complete within these physiologic concentrations. Three children responded to thiamine therapy with a reduction in concentration of plasma and urinary branched-chain amino and ketoacids. Each responder had at least 5% activity for branched chain alpha-ketoacid dehydrogenase in their mononuclear blood cells and in whole cell fibroblasts from cultured skin when compared to the activity in normal control cells. We propose that each child with maple syrup urine disease be assessed for their response to thiamine by quantifying the concentration of branched-chain amino acids in plasma before and after vitamin supplementation.
The subcutaneous space has received attention in recent years as a route for the continuous administration of drugs and implantation of drug delivery systems. Yet little work has been devoted to an examination of the mass transport (distribution) of drugs in the subcutaneous space and the factors that influence their rate of clearance. A mathematical model is developed to describe the spreading and resorption of substances infused into the subcutaneous space. It simulates radial diffusion and flow in the direction of spreading as well as lateral convection into the systemic circulation. An analytic solution is obtained for the distribution of the substance as a function of time and position in the subcutaneous space. Two independent parameters, v (Péclét no.) and H (generalized Biot no.), are found to control the transport. Examples are presented to illustrate the effects of these parameters on the distribution of substances in the subcutaneous space.
A factor which stimulates the aminoacylation of heterologous and homologous tRNAs for lysine and leucine, as well as a mixture of amino acids, has been isolated from cytoplasmic extracts in Drosophila. The stimulatory factor is separated from inorganic pyrophosphatase activity by DEAE-cellulose chromatography and from aminoacyl-tRNA synthetase activity by trichloroacetic acid precipitation. It contains no nucleotidyl transferase activity. It is trypsin-sensitive and heat-stable, indicating that it may be a small protein. Attempts to measure the molecular weight, however, indicate heterogeneity in size, ranging from 20,000 to 65,000. The A53g mutant has four times as much factor Ore-R adults at 0-2 days; by 6-8 days the level has declined to less than one and a half times that of Ore-R. The heightened aminoacylation activity in the mutant extract is accompanied by increased soluble protein levels. It is known that the stimulation of tRNA aminoacylation in A53g is controlled by modifier genes which enhance the expression of the A53g mutant. The possibility that the stimulation factor is a product of the modifier genes is examined.
The kinetics of drug release from a polymeric matrix originally proposed by Higuchi were extended for the case of high drug loading (relative to the solubility of the drug in the polymer). The model of a granular matrix in which an effective porosity and tortuosity are assumed to modify the normal Higuchi kinetics is reviewed. A new model, which allows the prediction of the kinetics of drug release from properties of the polymer and drug, is based on the assumption that the permeability of the dispersed matrix is a function of drug loading.
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Homozygous tw32/tw32 mouse embryos, obtained from both spontaneously ovulated and superovulated T+/tw32 females mated to T+/tw32 males, have a lethal period which extends from the 8-12 cell stage to the late morula stage. Most of the homozygous mutant embryos die at the early morula stage and are characterized by excessive amounts of cytoplasmic lipid, mitochondrial abnormalities, binucleated cells and nuclear lipid droplets. The excessive cytoplasmic lipid and nuclear lipid droplets distinguish 35-50% of the embryos (presumably tw32 homozygotes) from their litter-mates prior to the lethal period. The remainder of the distinguishing characteristics appear in the later (8-cell to late morula) tw32/tw32 embryos in frequencies high enough to be considered phenotypic expressions of the mutant genome. The present study indicates that the non-complementary tw32 and t12 alleles are in fact separate T locus recessive alleles.
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