Unraveling the mysteries of serum theophylline levels: a patient care report in the light of pharmacokinetics

One of our patients had trouble maintaining therapeutic and safe levels of theophylline, even though we were careful in planning and monitoring her drug regimen. This case report shows how we were able to use principles of pharmacokinetics to distinguish among plausible explanations for her experience. We discovered that she was not taking the drug consistently as prescribed and that supervised administration resolved apparent contradictions between doses and serum levels. We believe that physicians can use the same information and methods that we used to get better and safer results from theophylline therapy.     

Practical value of a new serum digitoxin assay

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.