Biomedical subjects
Publications and source records attributed to O Castro.
We have described a case of thrombocytopenic purpura caused by methyldopa. A methyldopa-dependent antiplatelet antibody as the mechanism of the patient's thrombopenia was suggested by a positive clot retraction inhibition test. This simple in vitro test should be done more often in suspected cases of drug-induced thrombocytopenia.
The survival characteristics of human sickle (SS) erythrocytes (RBCs) transfused to intact chimpanzees were determined. The mean post-transfusion recovery of 51Cr-labelled SS RBCs in four chimpanzees was 30.5% +/- 15.2 SD, and the half-life survival was 4.2 h +/- 0.8 SD. The recovery of control (hemoglobin AA) human red cells in five chimpanzees was complete and their mean intravascular T 1/2 was 22.3 h. Shorter survival of sickle erythrocytes was also shown by transfusing chimpanzees with mixtures of human cells such as 51Cr AA RBCs and 59Fe SS RBCs, or 51Cr SS RBCs and non-labelled fetal (cord blood) erythrocytes. The difference in survival of AA and SS RBCs resembles that in human recipients and was probably caused by sickling of SS cells in the chimpanzee circulation. These primate animals could, therefore, be used as a model for in vivo studies of sickle cell disease.
Overt iron deficiency was diagnosed in four patients with sickle cell disease. Three patients had homozygous SS and one had hemoglobin SC disease. The cause in each case was proved or suspected blood loss. Iron repletion was accompanied by increases in the blood hemoglobin and hematocrit levels, erythrocyte mean corpuscular volume, and mean corpuscular hemoglobin concentration (MCHC) and by change in the RBC morphologic characteristics from hypochromic microcytic to normochromic normocytic. The diagnosis of iron deficiency was confirmed by the finding of a low serum ferritin level, a high serum total iron-binding capacity, or both. Two patients who had had no painful crises while they were iron deficient began having crises again, and another patient had painful crises for the first time after the blood values improved. Whether a lowered MCHC is beneficial to patients with sickle cell diseases is an important but unanswered question.
This paper describes the use of a mobile health unit as a part of a community education, screening, and counseling program. By virtue of its mobility and more flexible hours, this model extends services into the basic urban, suburban, and rural community. Quality control of the diagnostic and counseling activities on the unit is maintained through supervision by the full-time staff of the Howard University Center for Sickle Cell Disease. The program is a part of the University Health Science complex which provides backup consultation and referral sources. The mobile health unit is equipped with a laboratory and waiting, education, and counseling areas; it operates in conjunction with a speakers bureau which conducts a significant portion of the community education. Referrals are made from the unit to a variety of community resources but primarily for additional education and counseling for sickle cell and follow-up services for elevated blood pressure and low and borderline hemoglobin levels.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of short-term cryopreservation on metabolic, functional, and survival characteristics of erythrocytes from patients with sickle cell disease was examined. Post-thaw hemolysis of glycerolized sickle (SS) erythrocytes was greater (mean 12.9%) than in hemoglobin-AA cells (mean 4.7%). Freeze preservation had no apparent effect on red cell morphology, percent irreversibly sickled cells, and fetal hemoglobin content. There were modest reductions in ATP and 2,3-diphosphoglycerate in thawed, washed sickle erythrocytes (12.7% and 29.7%, respectively). However, the autologous survival of 51Cr-labelled SS red cells was not shortened by cryopreservation. The safety and efficacy of autotransfusion of cryopreserved red cells in alloimmunized sickle cell disease patients with anemic episodes unrelated to sickling need to be determined.
Hemoglobin electrophoresis of cord blood from 4,499 newborns was performed as part of a sickle cell disease detection program. Although the expected frequency of the genes for hemoglobins S and C were observed, six newborns (five kindreds) were heterozygous for an alpha G Hb. In four kindreds, the alpha chain variant was identified as Hb G-Philadelphia. In each case, heterozygosity for this Hb was manifested at birth by the presence of Hb F/G (alpha 2 G gamma 2), a slow Hb migrating between the positions of Hbs S and C on cellulose acetate. In some newborns, Hb G (alpha 2 G beta 2) was also detectable, so that these cord bloods had four hemoglobin components: F, F/G, A, and G. The prevalence of Hb G-Philadelphia in this population sample is higher than that usually reported for black Americans and may represent a founder effect. Comprehensive screening of cord blood hemoglobins should use electrophoresis on alkaline media as the primary testing procedure because it allows recognition of most variants, such as the D (G) hemoglobins. Reliable identification of Hbs S and C requires citrate agar electrophoresis as a confirmatory test.
A patient with sickle cell beta+-thalassemia had thrombocytosis and erythrocytosis due to a myeloproliferative disorder best classified as polycythemia vera. RBC counts were 6 to 8 million/cu mm and the red cell mass was 33 ml/kg. A higher red cell mass and an increased hematocrit value were prevented probably by factors related to the hemoglobinopathy, such as microcytosis and hemolysis. The diagnosis of polycythemia vera in patients with sickle cell disease may be difficult to document and the association of these disorders has not been previously reported. This patient's high red blood cell and platelet counts did not result in recurrent vasoocclusive crises.
The recovery and survival of small quantities of 51Cr-labelled human erythrocytes (RBCs) transfused to nonhuman primates were measured. In two chimpanzees all of the human RBCs circulated 15 min after transfusion and were subsequently removed from the animals' blood with a half-life (T1/2) of 1.6 and 2.4 days. In baboons and rhesus monkeys over 95% of the human RBCs were cleared within 15 min after injection. Animal species, rather than antibody characteristics or titer, was an important determinant of the human RBC survival. Transfusion of human RBCs to chimpanzees can thus be explored as a test system to study human erythrocyte disorders.
Acute pulmonary complications of sickle cell anemia are sickle cell lung disease and bacterial pneumonias. Chronic abnormalities in lung function include a restrictive ventilatory defect and perhaps increased venous admixture to the pulmonary circulation. Coexisting sarcoidosis may complicate sickle cell anemia and interact to potentiate sickling. Sickle cell lung disease, or acute "chest syndrome," occurs with greatest frequency in adults, is due primarily to pulmonary infarction, and may lead to cor pulmonale. On the other hand, bacterial pneumonia due to Streptococcus pneumoniae occurs with greater frequency in infancy and childhood. Mycoplasma and other organisms may also cause pneumonia with protracted illness and slow resolution. Bacteremia and meningitis may be further complications, particularly in children. Precise diagnosis of the acute febrile pulmonary episode is often difficult. In adults the illness is commonly self-limited. However, a vigorous diagnostic approach is warranted in all severely ill patients.
The amino acid residues involved in the areas of contact that stabilise the haemoglobin S polymer fibre seem to be the same ones that stabilise the basic unit of the deoxyhaemoglobin S crystal: the Wishner-Love double strand. The haemoglobin S fibre is probably formed by a unique packing of these double strands.
Screening for sickle cell hemoglobin can detect carriers, who can benefit from education and genetic counseling, and can bring about early diagnosis, supportive care, and management for patients with established disease. However, such screening programs should be designed and supervised properly by health professionals to avoid methodological pitfalls and other unfortunate circumstances that have occurred in the past.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A child with homozygous sickle cell disease and transposition of the great vessels had erythrocytosis associated with markedly increased plasma erythropoietin activity. Her clinical course was complicated by neurologic manifestations but not by recurrent sickle cell vasooculsive episodes. The fetal hemoglobin level which had been greater than 25% during the first two years of life gradually decreased to less than 10%. She died at 3 years of age of congestive heart failure and severe anemia. The only sickle cell painful crisis occurred during her terminal illness. It is likely that the high levels of fetal hemorglobin decreased sickling and thus allowed erythrocytosis to develop. Fetal hemoglobin may also have prevented frequent vaso-occlusive events despite the high hematocrit level.
A guinea-pig model for study of the survival of human erythrocytes has been developed. The T1/2 survival of human erythrocytes in guinea pigs treated with ethyl palmitate and cobra venom factor is about 3 days. This model is particularly suited to the study of the pathogenesis and therapy of certain intrinsic red cell disorders, such as sickle-cell disease.
Erythrocytes (RBCs) from six patients with sickle cell anemia were transfused to laboratory rats in order to study the intravascular survival of irreversibly sickled cells (ISCs). Fifteen minutes after transfusion, a mean of 48.8 percent (range 23-95 percent) of the ICSs injected were present in the rats' blood, a value that was significantly lower than that for the total population of sickle cell anemia erythrocytes transfused (mean 82.4 percent, range 36-114 percent). The intravascular half-life of ISCs was also lower (mean 0.83 hours ± 0.18 SD) than that observed for the total sickle cell anemia erythrocytes (mean 1.62 hours ± 0.19 SD) during the initial two hours of the transfusion experiments. The irreversibly sickled cells that remained in the rats' blood thereafter survived as well as those cells that were not irreversibly sickled. Severe hypoxia in the recipient animals did not appear to selectively remove ISCs from circulation. These data are consistent with heterogeneity of ISCs in terms of their intravascular viability. Some ISCs may have adapted to the stress of circulation despite their abnormal shape.