Frank A. Oski

Occlusion of Large Cerebral Vessels in Sickle-Cell Anemia

Abstract Seven patients with sickle-cell anemia and neurologic deficits secondary to Central-nervous-system dysfunction were studied with cerebral angiography after careful preparation. Preparation of the patient reduced the level of S hemoglobin to less than 20 per cent before study, and all studies were performed without sequelae. Six of the seven patients were found to have partial or complete occlusion of large cerebral vessels. The internal carotid artery was involved in all six patients. Disease in the anterior and middle cerebral arteries as well as the vertebral artery was also observed. Two patients had repeat studies. The disease appeared to be progressive. These findings, rarely reported, indicate that the common clinical assumption that the Central-nervous-system manifestations of sickle-cell anemia are a consequence of exclusively small-cerebral-vessel obstruction may in fact be erroneous.

The effects of therapy on the developmental scores of iron-deficient infants†

To test the hypothesis that iron deficiency in infants and children is associated with behavioral alterations, 24 infants with iron deficiency anemia, ages 9 to 26 months, were randomly assigned to a treatment and control group. Bayley Scales of Infant Development were administered before treatment with intramuscular iron or placebo; the test was readministered in five to eight days. Children treated with iron showed a significant increase in their scores on the Mental Development Index averaging a mean gain of 13.6 points in a mean time of 6.8 days. The treated group was also found to become more alert and responsive and demonstrated improvement in tests of gross and fine motor coordination. These findings support the hypothesis that iron deficiency in infants produces developmental alterations and that these changes are rapidly reversible with iron therapy.

A Simple Nonradioisotope Technic for the Determination of Platelet Life-Span

Acetylsalicylic acid was shown both in vivo and in vitro to prevent the platelet lipid peroxidation normally induced by the aggregating agents thrombin and epinephrine, and the sulfhydryl inhibitor N-ethylmaleimide. After aspirin ingestion, there was a significant reduction (p smaller than 0.005) in platelet lipid peroxidation, with a gradual return to base-line values over a 10-day period. With these values, a normal platelet survival curve was constructed with a mean half-life of 4.4 days (range of 2.9 to 5.9 days). These values agree with the standard 51-Cr survivals in three patients with chronic idiopathic thrombocytopenic purpura. Half-lives of 1.0, 2.5, and 4.1 days by lipid peroxide technic compared with 1.9, 2.5, and 3.9 days by the concurrent use of 51-Cr. Thus, the technic may be used to measure platelet survival.

Postnatal Changes in Oxygen Transport of Term, Premature, and Sick Infants: The Role of Red Cell 2,3-Diphosphoglycerate and Adult Hemoglobin

Extract: In view of previous studies which did not show a precise relation between the percentage fetal hemoglobin and the position of the oxygen hemoglobin equilibrium curve, this problem was reexamined taking into account both the concentration of fetal hemoglobin and the 2,3-diphosphoglycerate (2,3-DPG) content of the cell.Forty-eight normal infants weighing 2500 g or more at birth were studied on days 1 and 5 of life and then at 3 and 6–9 weeks, and at 3–4, 5–6, and 8–11 months of age. Fifty-six ingfants ranging in birth weight from 900 to 2420 g were studied during the first 8 days of life and then at 2− to 3-week intervals until approximately 16 weeks of life. Twelve premature infants who were ill with the respiratory distress syndrome were also studied.Laboratory procedures consisted of measurement of total hemoglobin, fetal hemoglobin, red cell 2,3-DPG, and oxygen equilibrium curves.The “functioning DPG fraction” in millimicromoles per milliliter red blood cells (RBC) was obtained by multiplication of the total red cell DPG content (millimicromoles per milliliter RBC) by the percentage of adult hemoglobin.These studies confirm previous observations that the term infant begins life with blood that has an increased affinity for oxygen. During the first few months of life the oxygen-hemoglobin equilibrium curve gradually shifts to the right and between 4 and 6 months of age becomes similar to that observed in the normal adult.The change in P60 in these infants correlated neither with the change in red cell DPG content alone nor with the decline in fetal hemoglobin alone. Instead, the progressive decrease in oxygen affinity during the first 6 months of life correlated significantly (r = 0.876, P < 0.001) with the functioning DPG fraction. The term “functioning DPG fraction” is suggested to reflect the fact that both the DPG concentration and the adult hemoglobin concentration within the cell, with which the DPG interacts, are necessary factors in determining the position of the oxygen equilibrium curve.Infants with respiratory distress appear to have P50 s that are lower than those of healthy infants of similar gestational age and birth weight. This appears to be primarily a result of a decrease in red cell DPG concentration. It is this type of infant who may benefit from exchange transfusion with fresh adult blood.

Red-Cell 2,3-Diphosphoglycerate Levels in Subjects with Chronic Hypoxemia

Recently, Benesch et al.1 , 2 and Chanutin and Curnish3 demonstrated that the affinity of a hemoglobin solution for oxygen may be decreased by its interaction with organic phosphates. Both 2,3-diph...

Role of Dietary Iron and Fat on Vitamin E Deficiency Anemia of Infancy

Thirty-five infants weighing less than 1500 g at birth were fed four commercial formulas (A-D) varying in polyunsaturated fatty acid composition (32 per cent linoleic acid in A and B and 12 per cent linoleic acid in C and D) and in iron content (smaller than 1.0 in A and B; 12 to 12 mg per liter in B and D). Infants receiving formula B showed significantly lower hemoglobins (p smaller than 0.01) and higher reticulocyte counts (p smaller than 0.005) than infants fed the other three formulas. Infants receiving the two formulas with higher concentrations of unsaturated fatty acids (A and B) showed significantly greater hydrogen-peroxide-induced hemolysis (p smaller than 0.001) than those given diets containing lower amounts. Infants in groups A and B also had lower serum tocopherol concentrations. Infant red-cell membranes are altered by the increased amounts of polyunsaturated fatty acids and iron in the diet. It appears that the development of vitamin E deficiency anemia occurs in infants receiving iron supplementation.

Congenital Hemolytic Anemia with High Sodium, Low Potassium Red Cells

Abstract Evaluation of the erythrocytes of a child with hemolytic anemia of unknown cause showed that the intracellular concentrations of sodium and potassium were 100 mEq per liter of cells and 40...

Metabolic alterations in the human erythrocyte produced by increases in glucose concentration: The role of the polyol pathway

Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [(14)C]O(2) production from glucose-1-(14)C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide-adenine dinucleotide phosphate/reduced form of nicotinamide-adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cells normal substrate, glucose, can produce changes in red cell metabolism.

The Pocked Erythrocyte: Red-Cell Surface Alterations in Reticuloendothelial Immaturity of the Neonate

Abstract A study of red-cell surface morphology using interference-contrast microscopy showed striking morphologic differences in premature and term infants, children of various ages and normal adults. In normal adults 2.6 per cent of erythrocytes gave the appearance of having small (0.2 to 0.5 μ) pits or craters on their surface. By contrast, premature and term infants had a mean of 47.2 per cent and 24.3 per cent pitted cells respectively, reaching near adult values by two months of age in term infants and taking somewhat longer in premature infants. An inverse correlation was observed between birth weight and the number of pitted cells. The finding of increased numbers of pitted cells in the neonate may reflect reticuloendothelial or splenic hypofunction since this type of cell has so far been observed with such frequency only in patients without spleens.

δ-Aminolevulinic Acid Dehydratase Activity in Circulating Blood Cells: A Sensitive Laboratory Test for the Detection of Childhood Lead Poisoning

Abstract An inverse correlation was demonstrated between erythrocyte δ-aminolevulinic acid dehydratase activity and blood lead levels. δ-aminolevulinic acid dehydratase activity was shown to be a sensitive index of subclinical lead poisoning, more so than either urinary coproporphyrin or urinary δ-aminolevulinic acid. Enzyme levels were lower in children living in deteriorated slum housing of the inner city than in those living in better housing in urban and suburban areas. It is suggested that assays for this enzyme will serve both as a practical screening test for unrecognized plumbism among suspect populations and as an adjunct to the rapid diagnosis of acute lead intoxication.