One of the most useful methods available for the quantitative measurement of hemolytic rates in clinical subjects and for the evaluation of red cell viability after storage is based on the survival of transfused erythrocytes. Access to such data, however, has been restricted because of limitations in the methods hithertofore available for measuring red cell survival in vivo.The differential agglutination method of counting donor cells, the procedure most commonly employed, has limitations in that large transfusions are required;* the donor blood must be devoid of all antigenic isoagglutinins which are not likewise possessed by the recipient; the recipient's cells must contain agglutinogen A or B or M or a combination of the three agglutinogens which is not contained in the donor blood; and, finally, this method excludes the use of autotransfusion, which would eliminate the risk of transmission of hemologous serum jaundice.The labelling of donor cells with radioactive iron (Fe55) permits the conduct of survival studies on a short term basis (1-3) but re-utilization of radioactive iron released from hemolyzed donor cells and the subsequent incorporation of this label in the recipient's red cells preclude its use in studies extending for periods longer than 24 to 48 hours.

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Routinely processed, hematoxylin and eosin (H&E)-stained slides are typically used to assess the morphologic integrity of the central nervous system in neurotoxicity safety studies. However, the value of special stains for improving neuropathologic evaluations during the assessment of neurotoxicity has been emphasized in the neuroscience literature and by regulatory agencies. The primary objective of the present study was to characterize the spatial and temporal changes in neurons, astrocytes, and microglia after dizocilpine maleate (MK-801)-induced focal neuronal necrosis in the posterior cingulate/retrosplenial (PC/RS) cortex of the rat. A secondary objective was to evaluate the application of special stains and a novel sectioning procedure for detecting neurotoxicity. Sixty adult male Sprague-Dawley rats were treated with sterile water vehicle or 10 mg/kg MK-801 and perfused through the left ventricle (pumped at 65 mm Hg pressure) with 10% neutral buffered formalin or 4% paraformaldehyde at 4 hr and on days 1, 3, 7, 14, and 28 after treatment. For light microscopic evaluation, brain sections were stained with H&E, a special cupric-silver (CS) stain that selectively impregnates degenerating neurons and makes them readily evident, glial fibrillary acidic protein (GFAP) immunohistochemistry for astrocytes, and Griffonia simplicifolia isolectin B4(GSA) histochemistry for microglia. Brains perfusion-fixed with 4% paraformaldehyde were prepared for CS staining with a novel frozen-sectioning procedure for multiple embedding in a composite gelatin block. In H&E sections from treated rats, necrotic nerve cell bodies were observed in PC/RS cortical layers 3 and 4 on days 1, 3, 7, and 14, but not on day 28. These necrotic neurons required high magnification for detection (x20 objective, x10 ocular). In contrast, degenerating neurons selectively stained with CS were observed in the same location as necrotic neurons seen with H&E but at low magnification (x2 objective, x10 ocular). Cupric-silver staining showed details not seen with H&E, including dendritic and axonal degeneration with progressive fragmentation. Beginning on day 3, GFAP immunohistochemistry revealed hypertrophic astrocytes in a diffuse pattern throughout the region of cell body necrosis, a change that persisted throughout the study. However, GSA lectin histochemistry identified a few reactive microglia on day 1 in a multifocal pattern throughout the region of cell body necrosis. Reactive microglia were observed on days 3, 7, and 14, but not on day 28. Glial changes observed with H&E staining were limited to an increase in the cellularity of glial cell nuclei in the area of neuronal necrosis. This study provides a comprehensive and integrated view of the temporal changes occurring in neurons, astrocytes, and microglia during acute neurotoxic injury. Moreover, advantages for using new staining and sectioning methodologies to enhance the toxicologic evaluation of the central nervous system are demonstrated.

Iron absorption is a function of the gastro-intestinal mucosal epithelium. The normal non-anemic dog absorbs little iron but chronic anemia due to blood loss brings about considerable absorption—perhaps 5 to 15 times normal. In general the same differences are observed in man (1). Sudden change from normal to severe anemia within 24 hours does not significantly increase iron absorption. As the days pass new hemoglobin is formed. The body iron stores are depleted and within 7 days iron absorption is active, even when the red cell hematocrit is rising. Anoxemia of 50 per cent normal oxygen concentration for 48 hours does not significantly enhance iron absorption. In this respect it resembles acute anemia. Ordinary doses of iron given 1 to 6 hours before radio-iron will cause some "mucosa block"—that is an intake of radio-iron less than anticipated. Many variables which modify peristalsis come into this reaction. Iron given by vein some days before the dose of radio-iron does not appear to inhibit iron absorption. Plasma radio-iron absorption curves vary greatly. The curves may show sharp peaks in 1 to 2 hours when the iron is given in an empty stomach but after 6 hours when the radio-iron is given with food. Duration time of curves also varies widely, the plasma iron returning to normal in 6 to 12 hours. Gastric, duodenal, or jejunal pouches all show very active absorption of iron. The plasma concentration peak may reach a maximum before the solution of iron is removed from the gastric pouch—another example of "mucosa block." Absorption and distribution of radio-iron in the body of growing pups give very suggestive experimental data. The spleen, heart, upper gastro-intestinal tract, marrow, and pancreas show more radio-iron than was expected. The term "physiological saturation" with iron may be applied to the gastro-intestinal mucosal epithelium and explain one phase of acceptance or refusal of ingested iron. Desaturation is a matter of days not hours, whereas saturation may take place within 1 to 2 hours. We believe this change is a part of the complex protein metabolism of the cell.

The purpose of this study was to determine whether social work intervention would reduce nonemergent visits to the emergency department and increase scheduled pediatric visits. A high-risk repeater group of 104 pediatric patients with three or more emergency department visits was randomly selected to receive social work intervention. Control and intervention groups were compared for inappropriate emergency department utilization and scheduled primary care visits. Pre- and postintervention emergency department visits were significantly reduced in the intervention group compared with the group that received no intervention and with prior utilization. Scheduled visits declined in the control group but increased by 26 percent in the intervention group.

1. Application of the principles of hydrodynamics to the problem of blood flow and blood volume indicates that the calculation of blood volume and cell volume from the venous hematocrit and plasma volume (as determined by the dye method) is subject to considerable error. 2. This conclusion is borne out by determinations of total cell volume by viviperfusion and with the use of radioactive iron tagged erythrocytes, which have shown the erythrocyte volume to be only 70 to 75 per cent of the volume indicated by the previously mentioned calculations. 3. The average hematocrit of the entire vascular system is considerably lower than the hematocrit of the large vessels, and the cell-plasma ratio of the smaller vessels is still less. 4. In the dog there are no considerable stores of immobilized erythrocytes, and the total erythrocyte volume and circulating erythrocyte volume are identical. 5. The "rapidly circulating blood volume" can be determined by dividing the erythrocyte volume by the venous hematocrit, and is found to be considerably less than the total blood volume. 6. The concept of the "rapidly circulating plasma volume" is introduced, and it is found to be approximately 80 per cent of the total plasma volume. 7. The volume of plasma in the peripheral, cell free, sluggishly moving plasma films, plus that contained in small vessels in which no red cells are present, is also determined and found to be approximately 20 per cent of the entire plasma volume. 8. The existence and magnitude of these fractions of the blood plasma volume should receive consideration in studies of blood flow and blood volume.