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Biomedical subjects

A L Anderson

Publications and source records attributed to A L Anderson.

32 records · Page 2Linked to original sources

Echocardiographic diagnosis of right atrial thromboembolism.

In a patient with congestive cardiomyopathy who died suddenly from right ventricular thromboembolism, antemortem two-dimensional echocardiography demonstrated a right atrial mass with acoustic characteristics suggestive of a thromboembolus. These characteristics included an elongated structure that assumed multiple dynamic forms and lack of an intracardiac attachment point. Because of the high likelihood of right ventricular impaction of a cardiac embolus, an aggressive therapeutic approach to such lesions is advised.

Aged↗

Myelodyspoietic syndrome associated with diethylstilbestrol therapy.

We describe a patient with a myelodysplastic syndrome characterized by pancytopenia and an excess of myeloblasts in the bone marrow. He had received massive doses of diethylstilbestrol (150 mg daily) for seven years as therapy for prostatic carcinoma. Although myelodyspoiesis has been associated with other drugs, a relationship to estrogen therapy in man has not been reported previously. However, the administration of estrogens to animals has produced pancytopenia with a relative monocytosis and vacuolization of leukocytes. Examination of bone marroa, erythroid hypoplasia, and, with prolonged therapy, aplastic anemia. Further animal studies have demonstrated that estrogens exert a suppressive effect on marrow stem cells and granuloid progenitor cells. These experimental observations suggest a possible role of estrogens in the genesis of the hematologic changes we observed.

Aged↗

Development of an automated form generating system for menu item data.

At the University of Missouri-Columbia, an Automated Form Generating System consisting of six computer programs was developed to generate the master menu, production forecast and usage forms, production worksheet, food order report, and selective menus for patients. In the initial testing of the programs, this computer-assisted system showed a 30 per cent reduction in time requirred by dietitians and clerks when compared with the manual system. Some expected benefits include ease in making menu changes, substantial reduction in errors, automatic updating of documents, and reduction in storage space for forms because documents will be generated just prior to a production week. The system will be implemented at a later date.

Computers↗

An improved method for conjugating monoclonal antibodies with N-hydroxysulfosuccinimidyl DOTA.

A simple, water-soluble procedure for conjugation of monoclonal antibodies to 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) has been improved by optimizing pH, buffer, and temperature conditions for the preparation of N-hydroxysulfosuccinimidyl DOTA and its conjugation to the human/murine chimeric anti-carcinoembryonic antigen antibody cT84.66. This improved method results in a 6-fold increase in conjugation efficiency, a 3-7-fold decrease in antibody cross-linking, a more homogeneous population of conjugate species, and a 5-fold decrease in the quantities of reagents needed for conjugation. The cT84.66-DOTA conjugate was labeled to high specific activity with 111In, 90Y, 88Y, 64Cu, and 67Cu, affording near-quantitative incorporation of the majority of these radiometals. This improved conjugation procedure facilitates large-scale production and radiometal labeling of cT84.66-DOTA for clinical radioimmunotherapy trials.

Animals↗

Metabolism and renal clearance of 111In-labeled DOTA-conjugated antibody fragments.

Radiometal-labeled antibody fragments are promising reagents for radioimmunotherapy due to their high tumor uptake and rapid pharmacokinetics, but their therapeutic potentials are limited by high uptake and retention in the kidney. Identification of metabolic products is a first step in designing rationale approaches to lower kidney uptake. Previous studies in rats have shown that 111In-labeled DTPA-conjugated antibody fragments (via lysine residues) were degraded to an DTPA-epsilon-amino-lysine derivative and retained in the lysosomal compartments of the liver and kidney [Rogers et al. (1995) Cancer Res. 55, 5714s-5720s]. To determine the metabolic profile of another widely used metal-chelate, [111In]DOTA conjugated to lysines in antibody fragments via active ester chemistry, we analyzed kidney homogenates from nude mice injected with an [111In]DOTA-Fab generated enzymatically from the anti-lymphoma intact antibody Rituxan. The major kidney metabolite was identified as [111In]DOTA-epsilon-amino-lysine by comparison to an authentic synthetic standard. This end product was also identified in the urine, along with relatively small amounts of [111In]DOTA-Fab. Since injection of [111In]DOTA-epsilon-amino-lysine into nude mice resulted in rapid clearance into the urine without kidney retention, it is likely that the renal retention observed was due to kidney uptake of [111In]DOTA-Fab, followed by lysosomal degradation to [111In]DOTA-epsilon-amino-lysine, which is only slowly cleared from this compartment. This observation is supported by autoradiographs of the kidney showing rapid localization of radioactivity into the distal regions of the kidney cortex. To extend this analysis to clinical trials, we have also analyzed urine taken from a patient injected with the intact antibody [111In]DOTA-cT84.66. In that example, we found that the major radioactive species was also [111In]DOTA-epsilon-amino-lysine.

Animals↗