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F W Schultz

Publications and source records attributed to F W Schultz.

27 records · Page 2Linked to original sources
PubMed1988

New method for the analysis of flow cytometric data.

A numerical method for deriving the fractions of cells in different phases of the cell cycle from a single observed DNA histogram is presented. The observed histogram is regarded as a polluted version (containing allocation errors) of the true histogram. A mathematical model is used to describe the pollution process. A theoretical histogram, representing the true histogram, is constructed so that G1 cells are put into one channel and G2M cells into another; the distribution of S cells in between is approximated with a set of harmonic functions. This theoretical histogram is subsequently disturbed with Gaussian dispersion functions to stimulate the pollution, yielding a predicted histogram. Using a maximum likelihood estimation technique, the model parameters are adjusted iteratively, matching the predicted histogram to the actually observed one. With the final parameter values substituted, the corresponding final theoretical histogram is regarded as a reliable reconstruction of the true histogram. From the latter, the required percentages can be read directly. The advantage of this approach over other mathematical analysis methods is that it allows a wide range of different, continuous distributions for relatively few model parameters (thus featuring flexibility and realism and a diminished risk of encountering computational problems). In addition, estimation errors providing a measure of accuracy can be obtained. To test the method, it was used to analyze various observed histograms from the literature that have been obtained by either simulation or actual flow cytometric measurements. The method appeared to perform well, as compared to the reported results of several other methods of analysis applied to the same data.

Cell Separation↗
PubMed1987

Nonhomogeneous distribution of leukemia in the bone marrow during minimal residual disease.

In a rat model (BNML) for human acute myelocytic leukemia the distribution of leukemic cells in bone marrow samples from various sites was investigated, using monoclonal antibodies (MoAbs) and flow cytometry. Rats were studied before chemotherapy as well as thereafter, ie, in the "minimal residual disease" (MRD) phase. Bone marrow from different types of bones was analyzed from each animal. Before treatment, the ratio of the measured extreme values (ie, highest/lowest value) for leukemic cell frequencies in bones from individual rats ranged from 3.7 to 11.7. During the MRD phase the ratios of the extremes ranged from a factor of 36 to more than 13,000 from one rat to another. The variability between bones of comparable size was estimated by studying the ribs from each individual animal. Within individuals the extremes differed by a factor of 1.2 to 4.0 before chemotherapy and from 2.4 to greater than 320 after chemotherapy. The variability within the marrow cavity of a single bone was determined by analyzing multiple samples from femoral bones cut into slices. The leukemic cell frequency appeared to vary considerably, ie, before treatment from 1.7 to 7.3 and during MRD from 4 to 28,000. The presented data may contribute to understanding the sometimes conflicting observations in leukemic patients. Improvement of methods for detecting MRD will not automatically lead to a more accurate estimation of the total tumor burden. The reliability of diagnoses based on the analysis of single bone marrow aspirates appears to be highly questionable.

Animals↗
PubMed1986

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in plasma and bone marrow of children receiving low-dose oral methotrexate.

The absorption, distribution, and elimination kinetics of low-dose p.o. methotrexate (MTX) were repeatedly studied in 19 children during maintenance treatment of childhood acute lymphoblastic leukemia. Plasma concentrations, urinary elimination, and bone marrow concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were monitored during 24 h following a routine p.o. dose (30 mg/m2) using high-pressure liquid chromatography. Significant interindividual variability was found in time to peak concentration (30-180 min), peak concentration (0.41-2.77 microM), and to a lesser extent the half-lives (t1/2 alpha: 32.8-86.1 min; t1/2 beta: 43.6-350.0 min; t1/2 absorption: 25.2-60.3 min) and plasma area under the concentration-time curve from zero to infinity (195.6-818.5 microM.min). Significant amounts of 7-OH-MTX were detected in plasma, with a mean area under the concentration-time curve from zero to infinity of 208 microM.min compared with 365.6 microM.min for MTX. High concentrations of 7-OH-MTX were present in bone marrow 24 h after oral MTX (15/19 patients) and were at least five fold those in plasma and three fold the concentration of MTX in bone marrow. In four patients occasionally neither MTX nor metabolite could be detected. Repeated examination of these pharmacokinetic parameters in plasma and bone marrow showed that the intraindividual variability was small.

Administration, Oral↗