Joseph Kochen

Lung Surfactants, Counterions, and Hysteresis

The wide hysteresis and low surface tension of lung extracts, as studied on a modified Langmuir-Wilhelmy surface balance, are dependent on the presence of subphase electrolytes. A possible mechanism for the hysteresis and its importance to the exchange of surfactants between the alveolar cell and the alveolar surface film are discussed.

Transformation of congenital neutropenia into monosomy 7 and acute nonlymphoblastic leukemia in a child treated with granulocyte colony-stimulating factor

A cytogenetically normal infant with Kostmann syndrome (severe congenital granulocytopenia) was treated with granulocyte colony-stimulating factor, which resulted in a rapid improvement in his neutrophil count and a resolution of recurrent infections. After 11 months of therapy, splenomegaly developed, with thrombocytopenia, anemia, circulating nucleated erythrocytes, and acquired monosomy 7, which evolved during a period of 7 months into acute nonlymphoblastic leukemia. The use of granulocyte colony-stimulating factor in patients with congenital marrow failure disorders may induce or hasten the onset of a malignant transformation.

Levels of Lead in Blood and Hematocrit: Implications for the Evaluation of the Newborn and Anemic Patient

Extract: The uptake of lead was evaluated in vitro at hematocrits between 1% and 65% and at concentrations of lead in blood up to 1,000 μg/100 ml. Total erythrocyte volume was not a significant limiting factor in uptake of lead by erythrocytes at levels of lead in blood below 250 μg/100 ml at hematocrit 25%, below 375 μg/100 ml at hematocrit 41%, and below 500 μg/100 ml at hematocrit 65%. At a level of lead in blood of 80 μg/100 ml, erythrocyte volume was not a limiting factor at hematocrits above 10%. The diffusion of lead from a compartment which contained plasma or blood into another compartment which contained blood at hematocrits between 26% and 68% was studied. At equilibrium, the uptake of lead in blood was not reduced at the lower hematocrits.Lead was injected into rats with hematocrits between 31% and 68%, as a result of removal or transfusion of erythrocytes. Uptake of lead by blood did not correlate with hematocrit (significance of correlation coefficient >0.05). Rats were exposed to lead during gestation, lactation, and for a subsequent 4-month period. This resulted in a fourfold elevation of levels of lead in blood (38.9 ± 9.9 μg/100 ml as compared with control values of 9.6 ± 3.8 μg/100 ml). No correlation between hematocrit and levels of lead in blood could be established (correlation coefficient 0.20, P > 0.05). Lead acetate in doses of 50 μg and 75 μg was injected into the yolk sacs of 4-day chick embryos and lead in blood and hematocrit levels were determined 14 days later. Increasing amounts of injected lead resulted in increasing levels of lead in blood (9.0 ± 2.7 μg/100 ml in controls; 19.2 ± 7.4 μg/100 ml at 50 μg, and 32.5 ± 11.7 μg/100 ml at 75 μg). Despite the differences in levels of lead in blood, no relation between hematocrit and lead in blood was found (correlation coefficients of 0.25, P > 0.05 and 0.11, P > 0.05). Lead in maternal and newborn infant blood and hematocrit levels were determined. Despite the difference in hematocrit between infants (64.3% ± 9.8%) and mothers (37.5% ± 3.6%), there was no significant difference between levels of lead in infant blood (19.1 ± 7.6 μg/lOOml) and in maternal blood (17.0 ± 5.6 μg/100 ml). A positive correlation was found between levels of lead in infant and maternal blood (correlation coefficient of 0.58, P < 0.01). No correlation could be demonstrated between hematocrit and levels of lead in blood among infants (correlation coefficient 0.22, P >0.05) or among mothers (correlation coefficient 0.24, P > 0.05).Speculation: It has been assumed that the clinical evaluation of a given level of lead in blood requires correction for anemia. This was based on the assumption that the uptake of lead by the blood is limited by the reduced circulatory erythrocyte volume. This study has shown that the erythrocyte is present in considerable excess in the lead-erythrocyte interaction within the commonly encountered range of hematocrit and levels of lead in blood. This would indicate that hematocrit variation has little influence on uptake of lead by blood and that correction of levels of lead in blood for anemia is unnecessary. The presence of similar levels of lead in blood for neonates and mothers indicates that an equilibrium exists between levels of lead in fetal and maternal blood which is unaffected by the difference in fetal and maternal hematocrits. This suggests that the extent of lead exposure and the lead burden in soft tissue may be similar in the mother and fetus.

LASER-INDUCED MICROVASCULAR THROMBOSIS, EMBOLIZATION, AND RECANALIZATION IN THE RAT.

Intravascular thrombus formation has long been regarded as a process that involves an interaction between the blood stream and an altered inner blood vessel Thrombogenesis, as visualized microscopically in the living animal, has been produced experimentally by mechanical, chemical, and electrical injuries to blood vessel^.^-^ These diverse types of injury have generally been induced through the outer layers of the vessel wall and have resulted in a consistent reaction on the inner vascular surface. This has consisted of an adherence of blood cells, especially platelets, to the endothelium close to the site of injury, the adherence of cells to each other, and the development of a thrombus. It is the purpose of this presentation to describe a new approach to the production of localized microscopic lesions on the inner surface of selected blood vessels by means of an optically focused laser l 1 The development of the laser has made available an easily handled source of light energy of enormous intensity. The ruby laser emits a pulse of highly collimated coherent light that can be optically attenuated and focused to an extremely small spot. The high power density present for a fraction of a millisecond within a diameter of a few microns, suggests itself as a means for producing a highly localized injury to a selected target tissue.12. l 3

Diamond-Blackfan syndrome: an unusual cause of hydrops fetalis

An unusual case of Diamond-Blackfan syndrome whose initial presentation was hydrops fetalis is presented. Diamond-Blackfan syndrome and the pathophysiology of hydrops fetalis in severely anemic infants are briefly reviewed.

Hemolytic uremic syndrome associated with cisplatin therapy.

An adolescent with a small round cell tumor of the chest wall, who was treated with cisplatin, developed hemolytic uremic syndrome with severe hypertension, which ultimately contributed to her death. Cisplatins role as a possible causative agent of this syndrome is discussed. Recommendations are made for monitoring abnormalities that may signal the onset of this potential complication.

BRAIN LEAD LEVELS IN HEMORRHAGIC LEAD ENCEPHALOPATHY

Lead (Pb) encephalopathy in the newborn rat is characterized by hemorrhage restricted to the cerebellum. This was produced by giving 7 day old rats 0.5ml 1% 210Pb-acetate by gastric tube daily x 7. This resulted on day 14 in significantly higher Pb levels in the cerebellum than cerebrum (10.1 ± 4.0 vs 5.0 ± 1.2μg Pb/gm)(M ± SD). Since red blood cells (RBC) contain much Pb, it was unclear whether the higher cerebellar levels reflected extravasation of RBC or increased capillary permeability to Pb. This was resolved by labelling RBC by prior injection of 59Fe and quantitation of RBC trapping in brain. Pb administration resulted in a significant increase in RBC sequestration in the cerebellum (from control levels of 10.1 ± 1.1 to 49.3 ± 27.8μl RBC/gm), but little change in the cerebrum (from 9.5 ± 1.0 to 10.9 ± 1.1μl/gm). This increased retention of RBC accounted for 62.7 ± 24.2% of the Pb in the cerebellum and 29.1 ± 7.9% in the cerebrum. The remaining Pb represented the actual concentration of Pb in cerebellum (3.6 ± 2.4μg/gm) and cerebrum (3.6 ± 0.9μg/gm). Thus, the level of Pb in hemorrhagic regions of the brain proved to be identical to that in unaffected regions. The restriction of hemorrhage to the cerebellum despite the uniform distribution of Pb in the brain indicates that the cerebellar capillaries are particularly vulnerable to the toxic effects of Pb.

Acridine Orange Potentiation of Actinomycin D Uptake and Activity

Acridine orange enhances the uptake of [3H]actinomycin D in disrupted and intact human lymphocytes, as measured by liquid scintillation and autoradiography. Proflavine, quinacrine, chloroquine, and ethidium bromide are not effective. In mice, acridine orange increases the capacity of actinomycin to reduce spleen weight. Type II acridine binding to DNA may be a prerequisite for actinomycin enhancement.

1493 COGNITIVE FUNCTIONS(CF) IN CHILDREN ON CHRONIC INTERMITTENT HEMODIALYSIS(H)

CF have rarely been studied in chronically uremic children. Six children on H were evaluated with 16 neuropsychologic tests pre, 12 and 24 hrs post dialysis. There were 5 boys and I girl II to 18 yrs old with duration of uremia 6 to 52 months. Mean pre-dialysis creatinine at the time of testing was 9.2mg% and the mean change post dialysis was -6.4 ± 2.1 mg%. Results, utilizing a Friedman two-way analysis of variance, revealed that 6/16 measures changed significantly and the Walsh test showed differences between each of the three time periods. + = improved, O = no changeSimilar changes were not observed in 6 age and sex matched normal children. The results indicate that uremia adversely affects selective higher cortical brain functions in children. The speed of central processing, particularly when coordination of visual and motor acts is required, is best at 24 hrs and least pre-dialysis. Attention and memory were more compromised at 12 hrs than at 24 hrs, despite increasing uremia,suggesting that rapid volume and/or electrolyte shifts contribute to decreased performance.

LEAD: TOXICITY AND TISSUE LEVELS IN THE EMBRYO

Lead (Pb) injected into yolk sacs of day 4 chick embryos results in progressive central nervous system(CNS) bleeding which subsides by day 10-12 and is followed by the development of hydrocephalus. The use of Pb 210 permitted a correlation between the dose of Pb, tissue Pb levels, morbidity, and mortality. Increasing the Pb dose resulted in increasing CNS damage, mortality, and increasing concentrations of total body, blood and brain Pb. Injection of Pb after day 11 was accompanied by a marked decrease in morbidity and mortality. This was associated with reduced brain Pb concentrations, but no decrease in blood Pb levels. This indicates the development of a blood-brain barrier to Pb at this period in development and corresponds to the formation of specialized endothelial junctions in the CNS. Administration of Ca Edta at intervals after Pb injection on day 4 enabled delineation of the minimum period required for the occurrence of Pb toxicity. Edta given 2 minutes after Pb resulted in complete protection against Pb induced CHS damage and mortality. At intervals up to 8 hours there was a substantial diminution in morbidity and mortality. At longer intervals little protection was afforded by Edta. Blood and body Pb levels remained unchanged, irrespective of Edta administration; however, brain Pb levels increased with increasing Pb-Edta intervals. These results demonstrate a relationship between CNS damage and brain Pb levels and indicate that a brief exposure to Pb early in development suffices to produce CNS damage and embryo death.