Interactive computer-video modules for health sciences education.

Advances in electronic image recording and computer technology have resulted in a remarkable increase in the power and flexibility of interactive computer-video teaching systems. The University of Washington Health Science Videodisc Development Group first demonstrated a laser videodisc controlled by a remote central computer in 1980. Even this rudimentary unit highlighted basic medical informatics principles including: rapid accessibility; a "generic" or multi-purposed format; ease of computer control; and large collections of valid, rigorously reviewed images. Advances in medical informatics have led to the development of the following previously undescribed series of teaching units: 1. The hypertext programs Hypercard, Linkway, and Guide have been used with videodiscs to develop easy-to-use instructional and reference materials. These materials demonstrate the ease with which a computer-naive instructor may develop new programs and the advantages that the intuitive nature of these programs brings to student users. 2. Patient simulations using single and double screens plus pre-defined knowledge structures; 3. Interactive single topic tutorials using preset knowledge structures; 4. A key-word-based disc searching system; 5. Electronic video microscopy; 6. A series of programs developed independently by health science faculty who have purchased multi-purpose videodiscs that demonstrate the flexibility of the multi-purpose or "generic": collection concept.

[Calculation of direct standard costs in the evaluation of new technologies: application to the treatment of acute myeloblastic leukemias]. / Calcul de coûts directs standards dans l'évaluation des technologies nouvelles: application au traitement des leucémies aiguës myéloblastiques.

Financial incidence of new technology can be approached through the utilization of "direct standard cost". This method allows actualization of prices and permits the integration of new procedures. It is applied to acute non lymphoblastic leukemia.

Facts and speculation about necrotaxis (chemotaxis toward a dying cell).

The name "necrotaxis" has been given to a special type of chemotaxis in which granulocytes and monocytes are attracted to cells in the process of dying. Microirradiation devices (conventional UV and laser) have been used to destroy a target cell. Immediately, leukocytes (neutrophils and monocytes) can be seen to advance towards the damaged cell and to engulf it. Hemoglobin and albumin coagulated in the microbeam are equally necrotactic. The presence of plasma does not seem necessary, as the phenomenon also occurs in a saline environment. The neutrophil nucleus is not necessary for necrotaxis, anucleated cytoplasmic fragments are capable of directionality, rosette formation around the dead cell and phagocytosis. Three specific points are briefly discussed: -- the nature of necrotactic substances -- the recognition mechanism of damaged cells and molecules -- the eventual role of necrotaxis in vivo.

Heat as a probe of centrosomal function: a phase-contrast and immunofluorescent study of human blood monocytes.

In normal human blood monocytes, the nucleus is indented by the centrosome, which excludes the phase-dense granules that are spread throughout the cytoplasm. Within this paranuclear region, the paired centrioles are marked by immunofluorescent staining with an anti-centrosome antibody directed against the pericentriolar osmiophilic material that appears to serve as microtubule-organizing centers (MTOCs). Congruent paired structures are seen in phase-contrast. Following heat treatment (45 degrees C, 9 min), granules are retracted about a less indented nucleus, and anti-centrosome immunofluorescence is absent or very weak, even though paired centrosomal structures remain at least as phase-dense as in controls. Immunofluorescent staining with antimicrotubule antibody is also essentially lost following heat treatment. These findings are consistent with a heat-induced lesion in the pericentriolar osmiophilic material, which may prove generally useful as a probe of centrosomal function.

[A new technic for the study of the physiology of erythrocytes: measurement of their deformability as a function of osmolarity. Results obtained by an automatized Ektacytometer in normal blood and in various hemolytic anemias]. / Une nouvelle technique d'étude de la physiologie des globules rouges: la mesure de leur déformabilité en fonction de l'osmolarité. Résultats obtenus par un Ektacytomètre automatisé sur du sang normal et dans différentes anémies hémolytiques.

A system has been added to the Ektacytometer to allow continuous variation and measurement of the osmolarity of the suspension medium from 50 to 500 mosm kg-1 permitting the analysis of erythrocyte deformability over a range varying from hypo- to hypertonicity. The curves are obtained automatically in 7 min. from a blood sample of 150 microliters. The "minimum index" observed in hypotonicity indicates that the cells are non-deformable at this point just preceding hemolysis. The osmolarity at which this index occurs provides a measure of the osmotic fragility of the sample. In hypertonicity there is a zero index, corresponding to non-deformable cells, which occurs at an osmolarity dependent on the original internal viscosity of the cells. This "null index" introduces the notion of erythrocyte resistance to deformation in hypertonicity. This new technique permits the evaluation of the erythrocyte response to various factors affecting their shape, internal viscosity or membrane flexibility. We present and discuss examples of curves obtained with normal blood before and after fractionation by density and after treatment with cystamine, as well as pathological bloods from two hemolytic anemias (hereditary spherocytosis and sickle cell anemia).

Sickle cell shape and structure: images and concepts (1840-1980).

I. First observations of "crescentic particles" in animals. II. The first five descriptions of sickle shaped red cells in man. III. Relationship of sickling to the state of oxygenation of the hemoglobin. a) Forerunners: the sickling is reversible. b) Discoverers: sickling as result of asphyxia. IV. Sickle cell trait ("latent sickling"). V. Presence of hemoglobin rod-like structures in sickle cells. a) Indirect evidence. b) Observation of the surface of the cells by electron-microscope shadow casting technique. c) Electron microscopy of the interior of the cells. VI. Irreversible sickle cells. VII. Heterogeneity of sickling disorders. a) Association with other hemolytic anemias. b) Non-Hb S sickling. c) Factitious sickle cell shapes. VIII. Myelin forms and agglutination of sickle-cells. IX. Sickle cell shapes. a) Drepanocytes: mechanism of formation. b) Discodrepanocytes (holly-leaf forms). c) Echino-drepanocytes. d) Stomato-drepanocytes. e) Sphero-drepanocytes.

Quantitation of red cell deformability during progressive deoxygenation and oxygenation in sickling disorders (the use of an automated Ektacytometer).

1. The Ektacytometer, which allows quantitation of cell fluidity under known environmental conditions, has been recently modified so that cells can be exposed to any desired O2 tension during shear stress. 2. Heterozygotes (HbAS)show a pO2 vs deformability curve which varies from patient to patient in relation to the quantity of HbS. In the high viscosity medium used for this measurement, erythrocytes are normally deformable at any pO2 from 5 mmHg to normoxic conditions, at physiologic pH [7.3] and osmolarity (290 mOsm Kg-1). Modulation of the pH and osmolarity induces cell rigidity at different pO2 below 40 mmHg. 3. Homozygotes (HbSS) blood contains heterogeneous erythrocyte populations from the reticulocytes to abnormally dense cells (heterogeneity in cell volume, Hb concentration, shape, etc.). After separation by differential centrifugation, the various fractions each show a characteristic response to pO2 changes, pH, osmolarity and other parameters, which are specific to each patient and his pathological status at a given time. 4. This method was used to evaluate the activity of anti-sickling drugs. In addition, the action of such compounds on normal cells gives information on the mechanism of activity (changes in volume, in oxygen affinity, membrane properties or other--yet poorly explored--parameters). 5. This new application of the Ektacytometer may be of value for a) evaluating anti-sickling drugs and designing new therapeutic modalities, b) monitoring therapy of sickle cell patients, and c) research into the phenomenon of sickling.

Discovery of the red blood cell with notes on priorities and credits of discoveries, past, present and future.

A review of the earliest publications and letters of the scientists who have received credit for the first description of red cells illustrates the philosophical and practical difficulties of assigning priorities for discoveries. A knowledge of the scientific and cultural ambience of the day, of reports of scientific contemporaries or predecessors, both partisans and adversaries, and other background information illustrates how the consensus in crediting the discovery originated. However, the broader question remains: what are the proper criteria for assigning priority of discovery, yesterday, today and tomorrow?

New optical technique for measuring erythrocyte deformability with the ektacytometer.

The laser light scattered by erythrocytes subjected to a well-defined shear stess can be analyzed with the ektacytometer to obtain information regarding the changes in cell shape due to fluid shear. We describe an optical technique whereby an observed quantitative output derived from a mesurement of light intensity through a spatial filter is related to the change in cellular dimensions that were previously observed under similar fluid-shear conditions by use of microscopy and a cone-plate viscometer (rheoscope). We also present the predictions of a theoretical model (of the ektacytometer) based on approximations of light-scattering theory developed for nonspherical particles, and give preliminary results for the accuracy and sensitivity of this measurement of erythrocyte deformability. With this optical technique the instrumentation (ektacytometer) is made quite simple and suitable for use in the typical laboratory. This would allow a regular, quantitative assessment of this important blood cell quality, to supplement the data obtained from the complete blood count.

Automated ektacytometry: a new method of measuring red cell deformability and red cell indices.

The automated ektacytometer enables rapid measurement of red cell deformability by using small aliquots of blood (25 microliter). By subjecting red cells to varying shear stress in suspending media of different osmolalities, one can identify separate contributions of membrane viscoelastic properties, internal viscosity, and surface area-to-volume ratio to overall cellular deformability. The influence of drugs on red cell deformability can also be investigated. Analysis of the diffraction pattern of red cells that are aligned in the ektacytometer at minimal shear stress enables improved measurement of red cell diameter. Modern computerized image analysis can further improve the reliability of this measurement. Volume measurement of red cells of unusual shape is possible. since, under certain conditions, they transform into uniform ellipsoids in the ektacytometer. Aided again by improved image analysis, simple accurate computation of red cell volume becomes possible Ektacytometric measurement may provide a sensitive assessment of the overall functional integrity of living red cells or subpopulations of red cells. As such, these measurements are of research interest and may have major clinical utility.