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Biomedical subjects

O Castro

Publications and source records attributed to O Castro.

At least 73 records · Page 4Linked to original sources

Improved method for automated red cell exchange in sickle cell disease.

An improved method for intermittent-flow erythrocytapheresis in patients with sickle cell disease is reported. The method, a modification of the standard red cell exchange procedure for the Haemonetics 30S unit, dilutes with physiologic saline the patient's blood as it flows from the draw line and before it reaches the centrifugation bowl. The blood dilution (approximately 1.6 parts saline to 1 part blood) is used only during the first two passes, when the proportion of sickle erythrocytes in the patient's blood is still high. Only that amount of bowl supernatant (saline-diluted plasma) necessary to maintain extracorporeal volume below 500 ml is returned to the patient. The method described largely prevents the clumping of sickle erythrocytes in the centrifugation bowl, a complication frequently encountered with the Haemonetics 30S unit. Thus, changing the bowl between passes is avoided. Furthermore, the sickle red cells can be collected with the first pass and cryopreserved for possible future uses including the option of autotransfusion.

Adult↗

Acute splenic sequestration crises in adults with sickle cell disease.

Reports of acute splenic sequestration crises in adults with sickle cell hemoglobin C disease or sickle cell thalassemia are rare, although an enlarged and distensible spleen persists in half of these patients. Seven episodes of acute splenic sequestration crises in four adults, two with sickle C disease and two with sickle thalassemia, are described. The crises were life-threatening and recurrent in all, but there were no fatalities. One patient had mild steady-state thrombocytopenia suggesting hypersplenism. Technetium 99m/sulfur colloid scanning of the spleen during the acute splenic sequestration crises in three patients showed almost total lack of splenic uptake or decreased uptake with intrasplenic filling defects thought to be splenic infarcts or hematomas on follow-up computed tomographic scanning. The scanning abnormalities resolved following recovery from the crises. Acute splenic sequestration crises probably are common in adults with sickle C disease and sickle thalassemia but may be underdiagnosed or misdiagnosed as splenic infarctions. The hematologic and splenic findings during acute splenic sequestration crises resemble those following splenic vein ligation in animals.

Acute Disease↗

HLA-B35 is associated with red cell alloimmunization in sickle cell disease.

HLA-A, -B, -C, and DR antigens were determined in 33 patients with sickle cell disease (SCD), who had received red blood cell (RBC) transfusions. Twenty-one patients formed red cell alloantibodies after transfusions (responders) while 12 multitransfused SCD patients did not form any RBC antibodies (non-responders). We found that 67% of the SCD responder participants had HLA-B35 versus 25% of the non-responders (chi 2 = 5.3079, P = 0.0212). The frequency of B35 in non-responder SCD patients was similar to that of a normal healthy Black population consisting of 139 individuals. Calculation of the relative risk showed that sickle cell patients with B35 are six times more likely to form RBC alloantibodies after transfusion than those lacking that HLA antigen. We found no significant increase or association between any HLA-DR antigens and sickle cell disease.

Adolescent↗

Massive sequestration of human sickle cells after transfusion to a baboon.

A baboon was exchange-transfused with sickle cell anemia patients' blood. The animal died suddenly, and postmortem examination showed widespread red cell sequestration, particularly in the spleen and liver. The clinical and pathological findings were similar to those in children with sickle cell anemia who die of acute splenic sequestration syndrome. A control animal, exchange-transfused with normal human blood, tolerated the procedure without difficulties for a period of 4 days, when a delayed transfusion reaction occurred. Thus the baboon can be used as a model for the abnormal circulatory behavior of sickle cells and for the sickle cell sequestration syndrome.

Anemia, Sickle Cell↗

Perfluorocarbon compounds: effects on the rheological properties of sickle erythrocytes in vitro.

The effects of oxygenated perfluorotributylamine (Fluosol-43) on the rheological properties of sickle (HbSS) erythrocytes have been determined by means of microviscometry and positive pressure cell filtration. Incubation of deoxygenated sickled erythrocytes (pO2 congruent to 30 mmHg) with oxygenated Fluosol-43 reduced the percentage of sickled erythrocytes from about 63 to 33%. Deoxygenation of 40% suspension of sickle erythrocytes in autologous plasma increased the viscosity by about 160% at shear rate of 1.15 sec-1. Incubation of the deoxygenated sickled erythrocytes with oxygenated Fluosol-43 significantly reduced the viscosity at the low shear rates. Filtration of 0.2% suspension of deoxygenated sickle erythrocytes through capillary-sized Nuclepore filters showed high resistance at low flow rates. Oxygenated Fluosol-43 increased the deformability of HbSS erythrocytes and thereby reduced the resistance at flow rates less than 1 ml/min. These data suggest that perfluorocarbons may be useful in reducing the propensity of hemoglobin S polymerization and sickling and thereby prevent tissue infarction in vaso-occlusive crisis. Therefore, the concept of examining the potential application of perfluorochemicals for alleviating severe vaso-occlusive events may be useful.

Anemia, Sickle Cell↗

Distributions of hemoglobins A and S among erythrocytes of heterozygotes.

The recently developed capability to separate and quantify each of several proteins concurrently in single red cells presents an opportunity to test for biological variations in intercellular distribution of a protein as well as the extent of correlation between quantities of gene products derived from a single cell genome. In this preliminary study, erythrocytes from 30 sickle trait subjects were subjected to single cell electrophoresis and the resulting hemoglobin electropherograms were scanned by a recording densitometer. There was found to be heterogeneity among subjects in the form of the intercellular distribution of Hb S fraction, as tested by g statistics for skewness and kurtosis. Additionally, in all subjects there was statistically significant correlation between relative quantities of cellular Hb A and Hb S as measured concurrently in the same cell. These observations provide a basis for future research on the hypothesis that the form of the distribution of hemoglobin among erythrocytes is a heritable variable.

Analysis of Variance↗

Effect of a perfluorocarbon emulsion (Fluosol-DA) on reticuloendothelial system clearance function.

To study the effect of a perfluorocarbon oxygen transport emulsion (Fluosol-DA) on reticuloendothelial system (RES) function, we measured the blood clearance of human erythrocytes transfused to rats. Compared with saline treatment, Fluosol-DA at 30 ml/kg doses significantly increased both the percent 20-hour blood recovery (mean 8.9% +/- 2.7 SEM vs 1.3% +/- 0.25 SEM) and 51Cr t1/2 survival (mean 14.0 hours +/- 2.7 SEM vs 3.5 hours +/- 0.33 SEM) of the human red cells. This suppression of RES clearance function was transient and no longer detectable seven days after single Fluosol-DA doses. The Fluosol-DA-induced RES block was about three times greater than that obtainable with 4 g/kg of a soybean oil emulsion used for clinical hyperalimentation. On the other hand, the effect of ethyl palmitate (0.5 g/kg), a potent but toxic RES blocker, was 3.5 times greater than that of Fluosol-DA in this test system. If Fluosol-DA also induces RES block in humans, this emulsion could be explored as a therapeutic RES blocker in certain immune cytopenias.

Animals↗

Opsonization of pneumococci by whole serum from sickle cell disease patients.

An in vitro opsonic activity test was developed to measure the ability of whole serum from sickle cell disease patients to enhance the phagocytosis of Streptococcus pneumoniae by normal white blood cells. At the 30- and 60-minute incubation time periods, there was a 2- to 3-log reduction in the number of colonyforming units of S pneumoniae with both normal and sickle cell serum indicating opsonization of the organisms. However, the reduction in colony-forming units was significantly greater with normal than with sickle cell serum at both time periods (P <.0005 and P <.025 for the 30- and 60-minute time intervals, respectively). The sickle cell sera used in this assay were obtained from pediatric patients (age range, 1 to 15 years) and from adults (age range, 16 to 30 years). Based on this assay, sera from the adult sickle cell patients had a lower mean opsonic activity than that of the pediatric group. The significance of the lower opsonic activity in the adults with sickle cell disease is unknown and requires additional investigation.

Adolescent↗

Perfluorocarbon enhancement of heterologous red cell survival: a reticuloendothelial block effect?

The intravascular survival of human erythrocytes transfused to primate animals was prolonged by infusing the recipients with a perfluorocarbon red cell substitute (Fluosol DA). This effect is probably due to transient block of the animals' reticuloendothelial system by the perfluorocarbon emulsion. Perfluorocarbon compounds could be used to study the role of reticuloendothelial function in the immune destruction of red cells.

Animals↗

Sickle Lepore hemoglobin identified in a black American infant.

An integrated newborn infant screening, follow-up testing, and counseling service for hemoglobinopathies creates opportunity for early medical management of disease processes, assistance to parents in developing coping strategies, and educational counseling about recurrence risks in subsequent pregnancies. These objectives were operative in a case of sickle Lepore hemoglobin identified through a newborn infant screening service. The initial screening test was reported as Hb AS. Follow-up electrophoresis on cellulose acetate was compatible with Hb SS, but in citrate acid agar gel there were major and minor zones of S and A mobility, respectively. This and other hematologic parameters in both the child and his father were compatible with a sickle Lepore phenotype. This was supported by a tryptic peptide map of the purified variant hemoglobin from the father. Without a follow-up testing and counseling service, this case would probably have been missed until manifestation of clinical phenotype.

Anemia, Sickle Cell↗

Changes in cytosolic and nuclear estradiol receptors of normal Fallopian tube throughout the menstrual cycle.

During the normal menstrual cycle, the changes in estradiol binding to cytosol and nuclear receptors of ampulla, isthmus and fimbria were analyzed. Cytosol estradiol receptor concentration showed little variation throughout the cycle, but were higher at the periovulatory phases. The concentration of nuclear estradiol receptor markedly varied in isthmus and ampulla; being significantly higher at the late proliferative phase than at the secretory phases. A positive linear correlation between nuclear receptor content and plasma estradiol concentration was observed, while a negative one was found with plasma progesterone.

Adult↗