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Biomedical subjects

R Hillman

Publications and source records attributed to R Hillman.

18 recordsLinked to original sources

Platelet activation and aggregation during cardiopulmonary bypass.

Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.

Adenosine Diphosphate

The natural history of dilated cardiomyopathy--a community study.

The incidence, clinical features and natural history of dilated cardiomyopathy within a clearly defined population of Scotland was studied retrospectively. From 1982 to 1986, 57 cases were recorded in a population of 145,00, representing an annual incidence of 7.9 per 100,000 per year. This incidence rate is higher than that reported from other centres, and the overall survival rates were poorer.

Aged

Surveillance for persistent bovine viral diarrhea virus infection in four artificial insemination centers.

Four large bovine artificial insemination centers implemented a program of surveillance of resident and newly acquired bulls for persistent bovine viral diarrhea virus infection. Infection was identified in 12 of 1,538 bulls. Several clinical abnormalities, including acute and chronic mucosal disease, were evident among the persistently infected bulls. Semen produced by such bulls consistently contained bovine viral diarrhea virus, and such contamination was not always accompanied by diminished seminal quality. Infected bulls were detected by means of virus isolation tests performed on blood specimens, but not by use of serologic testing. Ten of the 12 persistently infected bulls were results of embryo transfer. Virologic surveillance of breeding herds, artificial insemination and embryo transfer centers, and the cattle trade is necessary to prevent spread of this virus by modern cattle breeding practices. Attention is also necessary to prevent contamination by this virus of the fluids used for recovery, in vitro manipulation, and transfer of bovine embryos.

Animals

Patient-side immunoassay system with a single-use cartridge for measuring analytes in blood.

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.

Hemoglobins

Syringe hazard.

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Humans

Computer-assisted drug assay interpretation based on Bayesian estimation of individual pharmacokinetics: application to lidocaine.

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.

Bayes Theorem

Thiamine response in maple syrup urine disease.

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.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

Ultrastructural studies of tw32/tw32 mouse embryos.

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.

Animals

Adult male victims of sexual assault: an underdiagnosed condition.

The records of 28 male victims of sexual assault were analysed retrospectively. The mean age at time of assault was 21.7 years and the mean number of assailants was 2.8. Sixteen victims (57%) reported skin or mucosal damage and 25 (89%) sustained penetrative anal intercourse. The threat of transmission of HIV was used by the assailant in 16 cases and sexually transmitted diseases, presumed consequent upon the attack, were found in 5 (18%). These observations suggest that male victims of sexual assault may be at particular risk of sexually transmitted infections, including HIV, and that efforts should be made to encourage them to come forward for help.

Adolescent