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Biomedical subjects

E S Gelsema

Publications and source records attributed to E S Gelsema.

At least 19 recordsLinked to original sources

A new representation of acid-base disturbances.

The acid-base status of intensive care patients is monitored on the basis of three quantities. The graphical representation which may be of help for the monitoring task is therefore cumbersome. The classical Siggaard-Andersen acid-base chart is such a representation, but it is only suited for evaluating one acid-base status at a time and not for representing acid-base paths. A new representation, obtained after a principal components transformation is presented. It is shown that the representation is characteristic for the laboratory instrument used. Its most attractive feature is that it is distortionless with respect to the three-dimensional configuration.

Acid-Base Imbalance

Energy-filtering transmission electron microscopy as a tool for structural and compositional analysis of isolated ferritin particles.

Structural and compositional analysis of isolated horse-spleen ferritin particles was performed by energy filtering transmission electron microscopy (EFTEM). Ferritin particles were collected in ultrathin (2 nm thick) chromium films and analyzed without any additional stain by electron energy-loss spectroscopy (EELS) for iron and carbon and by electron-spectroscopic imaging (ESI) for carbon. The ultrastructure of the proteinaceous shell of the ferritin particle, as obtained by the carbon net-intensity electron spectroscopical and carbon concentration-distribution images, was qualitatively compared to the structure as acquired by a negative-staining procedure. Quantitative analysis of the number of carbon atoms in the ferritin-shell proteins was carried out through an ESI-acquisition protocol and processing procedure with calibrated attenuation filters in the optical path to the TV camera. This procedure included images acquired with calibrated attenuation filters for the compensation of shading and the non-linear performance of the TV camera used in the analytical part of the procedure. A new ¿ESI-Spectra¿ program is proposed that allows element-related spectra to be generated at any place and with any frame size in a contrast-sensitive or other type of image present on the computer monitor screen.

Animals

A new model for diurnal blood pressure profiling. Square wave fit compared with conventional methods.

For the characterization of diurnal blood pressure variation, we developed a simple mathematical model that nevertheless does justice to the specific form characteristics of individual blood pressure registrations. Analysis was based on 24-hour continuous intra-arterial measurement of blood pressure obtained in 23 hospitalized patients with mild-to-moderate untreated essential hypertension (mean +/- SD, 112 +/- 13 mm Hg). The day-night difference for mean arterial pressure varied markedly (mean, 18.6 mm Hg; range, 6.8-36.0). Inspection of profiles suggested a model of blood pressure as two contiguous, complementary periods of constant pressure, a so-called square wave. Determination of the times of transience between both periods (segmentation) was performed individually using a least-square error criterion. Results were compared with those obtained by conventional methods, including analysis by Fourier modeling. The square wave fit accounted for a larger fraction (66%) of circadian variance of mean arterial pressure than modeling based on segmentation by visual inspection (59%, considerable observer bias) or by clock time (50%). Application of the Minnesota Cosinor Method resulted in the poorest description (47%). Segmentation based on harmonic modeling (61%) appeared to be cumbersome (10 harmonics needed), and the significance of additional information offered over the square wave fit is dubious. Observer bias makes segmentation by visual inspection unsuitable for assessment of the circadian variance of blood pressure. Even when daily activities are strictly regulated (hospital environment), circadian variance is not well modeled by clock time. As compared with harmonic analysis, square wave fitting is simple, and it appears to best model the circadian variance. The method can also be applied to data obtained from noninvasive ambulatory blood pressure monitoring.

Blood Pressure Determination

Correspondence analysis for quantification in electron energy loss spectroscopy and imaging.

Electron energy loss spectroscopy (EELS) is a technique to investigate the physical properties of material. Using this technique it is possible to detect the presence of a specific element in a specimen. When used in combination with an electron microscope, energy filtered images may be obtained, which in principle may be used to quantify the local element concentration. This involves a process of background correction, conventionally performed assuming a specific parametric behavior of the spectral intensity as a function of electron energy loss. In this article a parameter-free method is described for background correction based on the formalism of correspondence analysis. Such a method may be used in parts of the spectrum where the functional dependence of the spectral intensity is unknown. Use of this method for element detection has been suggested before. This article reports simulation experiments suggesting its suitability for quantitative determination of element distributions and element concentrations.

Image Processing, Computer-Assisted

Quantitative analysis of electron energy-loss spectra from ultrathin-sectioned biological material. I. Optimization of the background-fit with the use of Bio-standards.

A computer program for quantitative spectral analysis is proposed for the elemental analysis of biological material by electron energy-loss spectroscopy in a conventional transmission electron microscope, the Zeiss EM902. Bio-standards are used to test the performance of this program. The application of a simplex optimization method for curve-fitting is proposed to separate the ionization edge from the background. Making use of Ce-, Ca- and Fe-bio-standards, this method is compared with Egerton's well-known two-area method.

Calcium

Quantitative analysis of electron energy-loss spectra from ultrathin-sectioned biological material. II. The application of bio-standards for quantitative analysis.

Electron energy-loss spectroscopy (EELS) has been used to determine elemental concentrations in biological specimens, consisting of ultrathin-sectioned cells and tissues. Chelex100-based Ca- and Fe Bio-standards are used for elemental quantification to establish iron and calcium concentrations. These Bio-standards, as well as the biological materials, are treated in a standard EM procedure such that 'known' and 'unknown' sites are located in one cross-section. Uncertainties and variabilities present in the equations for calculating the concentration in the 'unknown' site (determined by comparing simplex-fitted EEL spectra from Bio-standards with those from tissue) are outlined in two examples. Using an H+ Bio-standard, the matrix composition of such biological cell material is analysed, leading to values which approach each other closely. Quantitative EELS, using Chelex100-based Bio-standards, is advocated.

Animals

Graphical non-linear representation of multi-dimensional laboratory measurements in their clinical context.

A polygon-based graphical representation of laboratory test results using nonlinear scaling is described. It is argued that the nonlinearity of the scale and the use of colors in the representation facilitates interpretation of the test result in its relationship to the standard reference range and critical clinical decision levels. Preliminary results suggest that this representation may be fruitfully used to enhance the efficiency of the information transfer from the clinical chemistry laboratory to clinicians. Other applications, inside as well as outside the medical field, may easily be imagined.

Chemistry, Clinical

Detection of aberrant observations in a background of an unknown multidimensional Gaussian distribution.

An exploratory iterative technique for the detection of aberrant observations on a background of a multidimensional Gaussian distribution is described. Its development was motivated by the analysis of a set of three measurements reflecting the acid-base metabolism in the blood of 2,402 intensive care patients. This new, three-dimensional treatment of such data yields a meaningful description. A technical evaluation of the method, using artificially generated data is also presented. It is shown that the model parameters of the underlying Gaussian distributions are determined with good accuracy and that the accuracy with which the contamination is estimated increases with increasing distance of the contaminating observations from the mean.

Acid-Base Equilibrium

Neutrophil granulation stained with May Grunwald Giemsa or pure Azure B-eosin Y quantified by image analysis.

Neutrophil granulation was quantified after staining with May Grunwald Giemsa or with the pure dyes Azure B and eosin Y. Spinner slides of the buffy coat of 3 normal subjects and 14 persons with different grades of toxic granulation were studied. Morphometric parameters were measured using an image analysis computer (Texture Analysis System, Leitz Wetzlar, FRG). The parameters for granulation varied over a wider range in Azure B (AzB) than in May Grunwald Giemsa (MGG) stained granulocytes. This is in accordance with the visual microscopy observation, that granulation is more pronounced after staining with AzB than MGG. The predominant shade of the nucleus was similar in both stains, whereas considerable and variable differences in the shade of the cytoplasm were found.

Azure Stains

Application of the method of multiple thresholding to white blood cell classification.

A new method of image segmentation based on the principle of multiple grey level thresholding has been applied to a data set consisting of 1149 white blood cells of 13 different, clinically important types, randomly chosen on 20 blood smears from leukemia patients. Classification of these cells on the basis of quantitative measurements in the segmented images yields an accuracy of 82.6%. Some of the erroneous classifications must be attributed to intrinsic problems in the assignment of a priori labels. Correcting for such cases, the performance of the method, as measured on the present data set, increases to 89.8%. This illustrates the practical applicability of the segmentation method in automated white blood cell and possibly other cytological and histological analysis systems.

Acute Disease

Quantitative radio-isotope cisternography for the investigation of CSF circulation in the posterior fossa and basal cisterns--a preliminary report.

In the absence of hydrocephalus there is an inclination to overlook enlargement of CSF spaces. In theory such enlargement might be the pathological basis for unexplained diseases seemingly related to disorders in CSF dynamics. By using Indium-111-DTPA in scinti-cisternography for 66 hours an attempt was made to identify such disorders by quantification of CSF circulation in the posterior fossa. The experimental data were fitted by means of two successive least square logarithmic regression analyses in order to make possible differentiation between "known" CSF disturbances and "external hydrocephalus". Theoretically, a biexponential curve would be expected. If therefore a monoexponential "best fit" is found, disturbances of CSF circulation may be taken to be present. For a definition of the features of normality in the case of a biexponential curve, however, further data on normal volunteers are needed.

Cerebrospinal Fluid

A model for the classification of specimens containing random proportions of abnormal cells.

The effect of abnormal cell proportion on the performance of an automated cervical prescreening system is discussed in K.R. Castleman and B.S. White, Cytometry 2:155-18. The model employed assumes fixed proportions of abnormal cells, both in the design stage and in the test stage. In the present paper, an extended model is developed that allows for random variability of this proportion. It is shown, that there is a fundamental, non-zero lower limit to the false-negative specimen error rate, which depends only on the coefficient of variation. This limit may be reached even for moderate values of the coefficient of variation, which implies that a satisfactory prescreening system may not be feasible.

Cytological Techniques

The use of correspondence analysis in the assessment of morphologic changes during carcinogenesis.

Correspondence analysis is a statistical technique originally developed for the analysis of frequency and contingency tables. It may also be successfully applied to the problem of the assessment of the characteristics of samples of cytological material. The present article describes the use of this formalism on feature data measured on urothelial cells in populations obtained from rats at different time points after exposition to a carcinogenic agent. After the application of correspondence analysis, the projections of the samples corresponding to the different time points onto the plane spanned by the first two factorial axes constitute a trajectory, preserving the time ordering. The locations of the projections of cell samples of untreated animals (controls) with respect to this trajectory suggest that two different processes inducing different morphological changes are at work: Early abnormal samples are characterized by a lower-than-normal value of nuclear stain content, whereas late abnormals are mainly characterized by a higher-than-normal nuclear stain value. It is shown that populations of selected atypical cells show less variation throughout the carcinogenic process than populations of randomly selected cells.

Animals

Classification of immature and mature cells of the neutrophil series using morphometrical parameters.

Quantitative morphological data of six classes of immature and mature cells of the neutrophil series of the bone marrow of normal persons were used for statistical classification experiments (myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands and segments). On each cell, parameters were measured directly from the image or calculated from the shape of the density histogram or the counting densitogram using a Texture Analysis System (E. Leitz, Wetzlar, Germany). The parameters were analyzed with the interactive statistical pattern recognition system ISPAHAN. One half of the data were used as a learning set and the other half as the test set. The parameters were compared according to their performance in discrimination between the classes, alone and in combinations. Parameters not contributing to an improvement of the discrimination were disregarded. Eleven parameters were selected and used for classification by two different methods: a stepwise and a "one-shot" method. Stepwise classification resulted in a 79% correct classification rate. Most errors occurred between cell classes in neighboring stages of maturation. In 96% of all cases the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. One step classification by the computer was in agreement with the technicians in 82% of the cases. For 98% of the cells the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. The data set was collected by two technicians, operating independently. Differences in their interpretation of the maturation stage were found by comparing the performance of classifiers based on both cell samples. Since the images of the cells were not available for reexamination, the causes of disagreement in classification between the technicians and between computer and technicians could not be evaluated.

Biometry