Biomedical subjects
Publications and source records attributed to W D Leslie.
The authors describe the radiographic-scintigraphic features of an unusual craniotubular dysplasia characterized by diffuse osteopenia with bone expansion and a "ground glass" appearance, markedly increased skeletal turnover, myelofibrosis, hypophosphatemia, and pigmented "coast-of-Maine" patches. This syndrome, termed panostotic fibrous dysplasia, is distinct from previously reported disorders.
Radionuclide imaging for the detection and localization of gastrointestinal bleeding is a highly sensitive and well-established clinical tool. 99Tcm-labelled erythrocytes have permitted the recognition of intermittent bleeding up to 24 h following injection. However, free pertechnetate is actively secreted by gastric mucosa and can result in confounding gut activity. The possibility that pertechnetate may elute from the radiolabelled erythrocytes was investigated in an in vitro model. Blood samples from five subjects undergoing gated cardiac studies were labelled by modified in vivo, modified in vitro and pure in vitro methods and then incubated in serum for 24 h. Automated cell counts and instant thin layer chromatography were used to measure the physical and radiochemical stability of the labelled erythrocytes. No detectable haemolysis occurred and no free pertechnetate was released from the cells. However, an unexpected hydrophilic 99Tcm species became detectable in the supernatant with a quantitative index which increased from an initial value of 0.016 +/- 0.004 to 0.079 +/- 0.012 at 24 h (P less than 0.00001). This index did not differ among the three labelling methods. A chromatographically similar material was identified in the urine of a patient undergoing a gastrointestinal bleed study. The possibility of gut and/or hepatobiliary secretion of this material needs further clarification before delayed positive studies can be relied upon to indicate gastrointestinal bleeding.
The process of developing and validating a quantitative test includes determination of a reference range. Traditionally this has been taken as the mean +/- 2 standard deviations for a random sampling from a reference population. However, this method fails to recognize the substantial variability in the sample mean and standard deviation for the small sample sizes frequently encountered in nuclear medicine. A new approach, which involves calculating confidence intervals for the upper and lower bounds of the traditionally defined range, recognizes three ranges of values: normal, indeterminate, and abnormal. The principles of this approach are illustrated using differential renal function in twelve renal transplant donors. The 99mTc-DTPA differential uptake between 1 and 2 min gave a traditionally-defined single-kidney range of 50% +/- 8%, whereas with our method the normal range would be 50% +/- 6% with indeterminate ranges of 37%-44% and 56%-63%. These values are consistent with the wide variation in reference ranges reported in the literature, and suggest that much of this variability may be a statistical artifact resulting from inadequate sample sizes. A nomogram has been derived that permits the power of the reference range determination to be easily calculated from the sample size. Analysis of the effect of sample size on the accuracy of the upper and lower bounds of the reference range is advocated whenever small reference populations are used.
Mathematical modeling of the AIDS pandemic has been limited by the difficulty of satisfactorily representing the marked behavioral heterogeneity that characterizes the various populations at risk. We propose an approach which models the spread of infection as a discrete-event simulation using SIMSCRIPT, a powerful simulation language. The program developed provides sufficient flexibility to adequately represent and study a wide range of risk-group dynamics. Using this tool we have verified the May-Anderson prediction relating contact rate heterogeneity to the rate of HIV spread. We have also been able to assess the sensitivity of the model to the particular choice of distribution for contact rates, disease stage durations, and intercontact intervals. It is thought that this approach will permit the empirical testing of hypotheses which do not lend themselves to a purely mathematical treatment.