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E Vichinsky

Publications and source records attributed to E Vichinsky.

69 records · Page 4Linked to original sources
PubMed1984

Evidence for a heterogeneous response to erythropoietin in the CFUE pool of human bone marrow.

To determine whether the CFUE pool within human bone marrow is heterogeneous with respect to erythropoietin (Epo) requirements, we studied CFUE growth in vitro as a function of Epo exposure time. We controlled the Epo exposure time by overlaying plasma clot cultures containing 0.5 U/ml Epo with an antibody prepared against human Epo. All cultures were grown for seven days. Benzidine-positive colonies containing eight or more cells were counted as CFUE. Colonies containing eight cells required at least 24-50 h of Epo exposure, and those containing 16 cells required at least 70-90 h of Epo exposure. After 50 h, the number of CFUE progressively increased until it reached a maximum at seven days of Epo exposure. These results suggest that the CFUE pool within human bone marrow is heterogeneous with respect to Epo requirements.

Bone Marrow Cells↗
PubMed1984

Evidence for the presence of CFU-E with increased in vitro sensitivity to erythropoietin in sickle cell anemia.

To investigate the cellular events that accompany erythroid hyperplasia, we studied several effects of erythropoietin (Epo) on marrow CFU-E in sickle cell anemia (SCA). We measured CFU-E number, CFU-E growth as a function both of Epo exposure time and of Epo concentration, and suppression of Epo-induced CFU-E formation by anti-Epo antiserum. With 0.5 U Epo/ml, the number of CFU-E was elevated in SCA (1,087 +/- 520) compared to normal (430 +/- 130). CFU-E were formed even when Epo was immediately neutralized by a 1/150 dilution of anti-Epo. After 40 hr of Epo exposure, only 2% of total CFU-E were expressed in normal marrow, whereas 12%-40% of CFU-E were expressed in SCA. Inhibition of CFU-E growth required at least 1/50 dilution of anti-Epo in SCA and a 1/300 dilution in normal marrow. In contrast to normal, a small number (5%-20%) of CFU-E were expressed in the absence of added Epo in SCA, and this pool required a 1/150 dilution of anti-Epo for inhibition. The Epo dose-response curve in SCA revealed a peak in colony formation around 0.1 U Epo/ml and 0.5 U Epo/ml, whereas only one peak at 0.5 U Epo/ml was seen in normals. These data strongly suggest that, in response to the demands of chronic erythroid hyperplasia in SCA, a pool of CFU-E is present characterized by increased in vitro sensitivity to Epo.

Anemia, Sickle Cell↗
PubMed1983

Iron deficiency in health and disease.

Iron deficiency is a common problem in otherwise healthy children and in children with systemic disease. We have reviewed the pathophysiology, laboratory diagnosis, and systemic effects of iron deficiency. We have emphasized that routine screening procedures do not efficiently predict those otherwise healthy children who will demonstrate a therapeutic response to iron. Furthermore, in patients with certain systemic diseases the diagnosis of iron deficiency is complicated by the inflammatory process and the response to a therapeutic trial of oral iron is often blunted. Since the potential adverse effects of iron deficiency may be extensive, a therapeutic trial of iron is indicated to establish the diagnosis of iron deficiency if the index of suspicion is high and laboratory results are equivocal.

Adolescent↗
PubMed1982

Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia.

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on the severity of their hemolytic anemia. We diagnosed alpha-thalassemia objectively by using alpha-globin-gene mapping to detect alpha-globin-gene deletions, studying 25 subjects with the normal four alpha-globin-genes, 18 with three, and four with two. The mean hemoglobin, hematocrit, and absolute reticulocyte levels (+/- S.D.) were 7.9 +/- 0.9 g per deciliter (4.9 +/- 0.6 mmol per liter), 22.9 +/- 2.9 per cent, and 501,000 +/- 126,000 per cubic millimeter, respectively, in the non-thalassemic group; 9.8 +/- 1.6 g per deciliter (6.1 +/- 1.0 mmol per liter), 29.0 +/- 5.0 per cent, and 361,000 +/- 51,000 per cubic millimeter in the group with three alpha-globin genes; and 9.2 +/- 1.0 g per deciliter (5.7 +/- 0.6 mmol per liter), 27.5 +/- 3.0 per cent, and 100,000 +/- 15,000 per cubic millimeter in the group with two alpha-globin genes. Deletion of alpha-globin genes was also accompanied by a decreased mean corpuscular hemoglobin concentration (MCHC) in post-reticulocyte erythrocytes and by increased hemoglobin F levels. The decreased intraerythrocytic hemoglobin S concentration and elevated hemoglobin F levels associated with alpha-thalassemia appear to diminish the degree of hemolytic anemia found in sickle-cell disease.

Adolescent↗
PubMed1982

Peroxidation, vitamin E, and sickle-cell anemia.

In summary, we propose the following scheme (Figure 5) to describe the role of peroxidation in the pathophysiology of SCA. Sickle erythrocytes are more susceptible to peroxidation than are normal erythrocytes. This increased susceptibility to peroxidation is, in part, due to decreased blood vitamin E levels and abnormal membrane phospholipid organization induced by sickling. The peroxidative damage of sickle erythrocytes may accelerate or contribute to loss of cell deformability and to chronic hemolysis. Peroxidative damage can produce abnormal cellular properties, such as potassium leak and reduced filterability, and contribute to formation of ISCs. Increased red cell rigidity can initiate episodes of capillary obstruction, leading to vasoocclusive painful crises and to tissue infarction. Liver dysfunction as well as increased production of bilirubin secondary to hemolysis could result in bile sludging and decreased secretion of bile salts into the intestinal lumen. Reduced bile salt secretion leads to partial fat and vitamin E malabsorption. Vitamin E deficiency enhances red cell susceptibility to peroxidation and promotes a vicious cycle in SCA. Although we have not studied factors that might initiate peroxidative damage, sickle hemoglobin and excess body iron should be considered as potential sources. Our studies suggest that vitamin E supplementation to sickle-cell patients could be of clinical benefit.

Anemia, Sickle Cell↗
PubMed1981

The diagnosis of iron deficiency anemia in sickle cell disease.

We determined the prevalence and optimal methods for laboratory diagnosis of iron deficiency anemia in patients with sickle cell disease. Laboratory investigations of 38 nontransfused and 32 transfused patients included transferrin saturation, serum ferritin, mean corpuscular volume (MCV), and free erythrocyte protoporphyrin (FEP). Response to iron supplementation confirmed the diagnosis of iron deficiency anemia in 16% of the nontransfused patients. None of the transfused patients were iron deficient. All iron-deficient patients (mean age 2.4 yr) had a low MCV, serum ferritin less than 25 ng/ml, transferrin saturation less than 15%, and FEP less than 90 micrograms/dl RBC. Following therapy, all parameters improved and the hemoglobin concentration increased greater than 2 g/dl. A serum ferritin below 25 ng/ml was the most reliable screening test for iron deficiency. There were 13% false positive results with transferrin saturation, 3% with MCV, and 62% with FEP. FEP values correlated strongly with reticulocyte counts. The high FEP was in part due to protoporphyrin IX and not completely due to zinc protoporphyrin, which is elevated in iron deficiency. We conclude that iron deficiency anemia is a potential problem in young nontransfused sickle cell patients. Serum ferritin below 25 ng/ml and low MCV are the most useful screening tests.

Adolescent↗
PubMed1980

Fetal Hb production during acute erythroid expansion. I. Observations in patients with transient erythroblastopenia and post-phlebotomy.

In order to study fetal haemoglobin production during acute erythroid expansion we did sequential measurements of Hb F-containing erythrocytes (F-cells) and of relevant haematological parameters in 10 subjects recovering from eyrthroid aplasia, iron deficiency anaemia or following phlebotomy. An increased production of F-cells was consistently observed during the acute marrow expansion, but there were significant differences in the maximum F-cell response among individuals. These differences could not be explained by differences in the degree of anaemia alone, nor could they be correlated with the level of peak reticulocytosis. Two patients who reached the highest F-cell numbers were probably carriers of heterocellular hereditary persistence of Hb F, suggesting that this gene may play a role in determining the magnitude of F-cell production in anaemic patients. It is speculated that the main reason for the consistently observed increase in F cell production during acute marrow expansion is the premature terminal differentiation of earlier erythroid precursos (burst forming units; BFUe). This proposition is in accord with observations in vitro which suggest that Hb F is expressed en eyrthroid clones derived from BFUne's. It is further proposed that differences in the degree of BFUe recruitment may underly the disparities in Hb F response among individuals subjected to similar anaemic stimuli.

Adolescent↗
PubMed1978

Immune response after splenectomy.

The immune response to intravenously administered bacteriophage phiX 174 and subcutaneously administered tridecavalent pneumococcal polysaccharide vaccine was studied in 31 patients with anatomical or functional asplenia. Antibody responses to primary immunisation with phiX 174 were significantly decreased while clearance was normal. Secondary responses were quantitatively normal; however, production of antibody did not switch from IgM to IgG as seen in controls. All groups of asplenic patients accept those patients with Hodgkin's disease demonstrated significant seroconversions in response to pneumococcal polysaccharide antigens. One patient with Hodgkin's disease, treated with local irradiation only, demonstrated normal responses to pneumococcal capsular antigens. 10 of the 12 capsular antigens for which antibody was measured stimulated threefold increases in antibody in the 26 asplenic patients without Hodgkin's disease, which is similar to that observed in controls. Since the majority of cases of overwhelming postsplenectomy infection are caused by Streptococcus pneumoniae, all patients with either anatomical or functional asplenia should receive pneumococcal polysaccharide vaccine.

Adolescent↗
PubMedDate not supplied

Nesidioblastosis in sickle cell disease.

Although the endocrine pancreas appears to play an important role in the pathophysiology of sickle cell disease, very little is known about the morphologic changes in this tissue. Our study was initiated to delineate the microscopic features of the endocrine pancreas in a large autopsy series of sickle cell hemoglobinopathies. From more than 650 cases archived at the Centralized Pathology Unit for Sickle Cell Disease (Mobile, AL), 224 autopsy cases were identified for review of clinical and gross autopsy findings and/or for microscopic studies, including histochemical stains (trichrome, reticulin, iron), and immunohistochemical stains (insulin, glucagon, somatostatin, and pancreatic polypeptide). The gross examinations were recorded as unremarkable in 65% of the autopsies. In childhood and adolescence (< or = 18 years), pancreas weights (50.76 +/- 5.16SE gm) were significantly greater (p < 0.0001) than age-matched controls (30.42 +/- 3.59SE gm). In adulthood, pancreas weights (108.34 +/- 5.29SE gm) were not significantly different from controls (110 gm). Microscopic findings included vascular congestion (48%), edema (65%), siderosis (31%), and nesidioblastosis (76%), which included islet cell dispersion (53%), hyperplasia (23%), and hypertrophy (25%). Analysis by age groups suggested that islet cell dispersion/hyperplasia persists unchanged, whereas diameters of compact islets tend to increase with age. These findings may be related to local tissue hypoxia and/or increased metabolic energy needs in sickle cell disease.

Adolescent↗
PubMedDate not supplied

Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S. pneumoniae among children with sickle cell anemia. The Ancillary Nasopharyngeal Culture Study of Prophylactic Penicillin Study II.

PURPOSE: To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia. METHODS: Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents. RESULTS: Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant. CONCLUSIONS: The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.

Anemia, Sickle Cell↗
PubMedDate not supplied

Tonsillectomy, adenoidectomy, and myringotomy in sickle cell disease: perioperative morbidity. Preoperative Transfusion in Sickle Cell Disease Study Group.

PURPOSE: To compare the rates of perioperative morbidity of patients with sickle cell anemia who were randomly assigned to 2 preoperative transfusion regimens and to identify predisposing factors for perioperative complications. PATIENTS AND METHODS: Investigators at 36 centers enrolled 118 patients who were scheduled to have elective surgery and agreed to randomization between 2 preoperative transfusion regimens. Forty-seven subjects were enrolled but not randomized, including 20 who were not transfused before surgery. Perioperative management was based on a prescribed care plan. RESULTS: Tonsillectomy and/or adenoidectomy (TA) were performed on 136 persons, and 29 had myringotomy as their primary procedure. There were no differences in the frequency of complications between the randomized groups. The serious, non-transfusion complication rates for randomized patients were 32% (34 of 107) for TA and 36% (4 of 11) for myringotomy. A history of pulmonary disease was a predictor of postoperative sickle cell-related events for patients undergoing TA surgery. CONCLUSIONS: The more intensive transfusion regimen did not result in fewer perioperative complications. The high frequency of complications emphasizes the need for anticipatory management of persons undergoing TA. A history of pulmonary disease identifies patients at increased risk for sickle cell-related events after TA surgery. Patients undergoing myringotomy have a low frequency of sickle cell-related events but a significant frequency of other serious perioperative complications.

Adenoidectomy↗
PubMedDate not supplied

Use of hydroxyurea in children ages 2 to 5 years with sickle cell disease.

The efficacy and side effects of hydroxyurea in young children with sickle cell disease are unknown. The authors followed-up eight young children (mean age 3.7 years) during therapy with hydroxyurea for an average of 137 weeks. Total and fetal hemoglobin levels rose with hydroxyurea therapy. Hospital admission rates and total hospital days decreased during hydroxyurea therapy. No unexpected toxicity occurred, and growth and development were unaffected. This pilot study suggests that hydroxyurea is safe and effective in young children with sickle cell disease.

Anemia, Sickle Cell↗
PubMedDate not supplied

Outreach strategies for Southeast Asian communities: experience, practice, and suggestions for approaching Southeast Asian immigrant and refugee communities to provide thalassemia education and trait testing.

This article outlines general strategies for outreaching to Southeast Asian immigrant and refugee communities with thalassemia education. Because of positive net migration and increased birthrates during the last 15 years, Asian Pacific Islanders are among the fastest growing populations in California. Dr. Fred Lorey of California Newborn Screening shows that 1 of 12 Southeast Asians is a carrier of hemoglobin E, demonstrating a particular need to outreach to these communities. The challenge of educating Southeast Asian populations include language barriers, differences in cultural and/or religious beliefs, geographic location, and unfamiliarity with and/ or mistrust of Western health care systems. In addition, outreach workers must consider the great diversity of ethnicity, language, literacy, and education levels, and degree of acculturation to the US within the Asian/Southeast Asian groups. It is crucial before embarking on any outreach campaign to understand the history and make-up of the target audience, including ethnic minorities and dialects, to translate written materials into appropriate languages or audio formats, and to have a group of trained interpreters for events. Additionally, a continuing education model for the outreach/medical staff is important to maintain robust understanding of these diverse communities. Specific strategies include using visual aids, medical professionals as authority figures, and bicultural high school and college students during presentations. Finally, establishing trust and maintaining a continued presence in communities are the most important aspects of a successful outreach campaign.

Asia, Southeastern↗
PubMedDate not supplied

Stem cell transplantation for sickle cell disease: can we reduce the toxicity?

Since the genetic basis of sickle cell anemia was discovered over 50 years ago, many therapies have been developed for the treatment of this disorder. Hematopoietic cell transplantation offers curative potential, but it is associated with a 5-10% risk of dying. Patients who undergo allografting but develop stable donor-host hematopoietic chimerism appear to experience a significant clinical benefit. Our paper discusses the risks and benefits of hematopoietic cell transplantation in patients with sickle cell disease and summarizes the outcome of 147 patients who received allografts for sickle cell disease. We also review the development of new approaches to establish stable mixed chimerism after transplantation for sickle cell disease.

Adolescent↗