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Biomedical subjects

Dan Richards

Publications and source records attributed to Dan Richards.

3 recordsLinked to original sources

Modification of a biventricular assist device to facilitate preservative infusion and organ recovery in a nonheart-beating donor.

A 46-year-old patient supported by a biventricular assist device (BiVAD) was transferred to our institution for evaluation for heart transplant. The patient was found to have a large intracranial hemorrhage with profound deterioration of neurologic status. The poor prognosis prompted the decision to withdraw care and pursue organ donation. Because the patient did not meet brain death criteria, nonheart-beating donor organ donation was pursued. After the termination of care, the BiVAD was modified: the left side to provide organ preservative solution and the right side to allow drainage. Eight liters of cold University of Wisconsin solution were pumped systemically over 10 minutes, the donor was drained, and the liver was harvested. This technique expedited donor perfusion by eliminating the need to cannulate, minimizing ischemic time for the liver. Although the recipient outcome was poor, and retransplantation was eventually necessary, we believe it was most likely not attributable to the quality of organ preservation. This report discusses the technical aspects of this potentially beneficial procedure.

Cadaver↗

Computational knowledge integration in biopharmaceutical research.

An initiative to increase biopharmaceutical research productivity by capturing, sharing and computationally integrating proprietary scientific discoveries with public knowledge is described. This initiative involves both organisational process change and multiple interoperating software systems. The software components rely on mutually supporting integration techniques. These include a richly structured ontology, statistical analysis of experimental data against stored conclusions, natural language processing of public literature, secure document repositories with lightweight metadata, web services integration, enterprise web portals and relational databases. This approach has already begun to increase scientific productivity in our enterprise by creating an organisational memory (OM) of internal research findings, accessible on the web. Through bringing together these components it has also been possible to construct a very large and expanding repository of biological pathway information linked to this repository of findings which is extremely useful in analysis of DNA microarray data. This repository, in turn, enables our research paradigm to be shifted towards more comprehensive systems-based understandings of drug action.

Algorithms↗

CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker of Alzheimer's disease.

Aging represents the greatest risk for development of Alzheimer's disease (AD), and changes in peripheral immune cell phenotypes have been found to be associated with aging. Using flow cytometry, we measured the relative expression levels of CD45 isoforms, a marker of nai;ve versus memory CD4+ T cell status, on isolated CD4+ T lymphocytes from patients with a clinical diagnosis of probable Alzheimer's disease, normal elderly, cognitively abnormal elderly, and patients with clinically diagnosed other forms of dementia. Data show significantly lower levels of CD45RA, and an increase in the CD45RO/CD45RA ratio, on CD4+ T cells in patients diagnosed with probable Alzheimer's disease (n=46) and in cognitively abnormal individuals (n=37) compared to age-matched normal participants (n=90). Patients diagnosed with other forms of dementia (n=19) did not significantly differ from normal individuals. Both CD45RA and the CD45RO/CD45RA ratio had higher positive and negative predictive values and were more sensitive biomarkers of probable AD than the apolipoprotein E epsilon 4 allele, and had greater predictive ability for probable AD by regression analyses. Additionally, a testing strategy employing apolipoprotein E genotyping and CD45RA or the CD45RO/CD45RA ratio revealed increased sensitivity, positive and negative predictive values, and predictive ability over the apolipoprotein E epsilon 4 allele. These data show altered peripheral immunity in AD patients, and raise the possibility that a testing strategy using CD45 isoform alteration on CD4+ T cells and apolipoprotein E genotype may be clinically valuable for diagnosing probable AD.

Aged↗