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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PURPOSE: To describe a case of spontaneous central retinal artery occlusion in a young man with hemoglobin sickle cell disease.METHOD: Case report.RESULTS: A 31-year-old African-American man with a history of hemoglobin SC (sickle C) disease developed sudden painless loss of vision in the right eye. Medical history was remarkable for the recent history of a mild sickle crisis, but no other systemic illness or contributing factors. Central retinal artery occlusion was diagnosed with retinal whitening, cherry red spot, and delayed arteriovenous transit on fluorescein angiography. Over the ensuing week, the patient had visual recovery to 20/60 in the absence of therapeutic intervention.CONCLUSION: Central retinal artery occlusion has been reported in sickle cell hemoglobinopathies (ie, SS, S-thal, sickle trait, and SC), but the association with double heterozygous SC disease is rare. Most reports have described additional contributing factors, such as trauma or concomitant systemic illness, to help account for the central retinal artery occlusion. The present case suggests that SC disease alone is sufficient for the development of central retinal artery occlusion.
Am J Ophthalmol 2000 Dec
PMID:Correction-spontaneous central retinal artery occlusion in hemoglobin SC disease(1) 1112 34

Several inherited diseases can now be treated using postnatal or prenatal, in utero, transplantation of stem cells from the human fetal liver. Twenty-four patients with severe immunodeficiency diseases have been treated in infancy and three at the fetal stage, in our institution. We have also treated similarly 34 patients with inborn errors of metabolism or hemoglobinopathies. A total of 64% of all patients are alive with either full cure of their initial disease or at least significant benefit from the treatment. Immunological reconstitution can develop despite full mismatch between the stem cell donor and the recipient patient. Tolerance is acquired both towards donor and host antigens. Gene therapy is starting its development in some infants with an immunodeficiency related to a known gene defect and, in the future, it may be used in fetuses, immediately after the prenatal diagnosis of the gene abnormality.
Int J Immunopharmacol 2000 Dec
PMID:Perinatal fetal-cell and gene therapy. 1113 10

Although the risk factors for stroke in children are numerous and differ greatly from the causes of stroke in adults, a thorough diagnostic evaluation can identify one or more risk factors in most patients. Cardiac disorders and hemoglobinopathy are the most common causes of ischemic infarction, whereas various congenital anomalies of the blood vessels or defects in coagulation or platelet function are often found in children with intraparenchymal hemorrhage. More than one risk factor is commonly identified, especially in children with dural venous thrombosis. Identification of the underlying risk factors for cerebrovascular disorders in children is important because many of the risk factors can be treated, reducing the risk of subsequent strokes.
Semin Pediatr Neurol 2000 Dec
PMID:Etiology of stroke in children. 1120 15

Monthly hemochrome parameters were obtained during the first 2 years of age in 22 children with perinatal human immunodeficiency virus type-1 (HIV-1) infection and in 58 exposed seroreverted children. Timing and predictive value of hemochrome modifications were investigated. Exclusion criteria were hemoglobinopathies and zidovudine (AZT) treatment in pregnancy. When AZT treatment was undertaken children were eliminated from the study. From the second month of life red blood cell (RBC) counts, hemoglobin (Hb) concentrations, and hematocrit values were significantly lower in infected than in uninfected children. RBC counts progressively diverged in infected and uninfected children, and mean values in the former group never reached 4.10(12)/L. No difference was observed in Hb content ratios and RBC size parameters. At 2 months RBC counts, Hb concentrations, and hematocrit values below reference values were associated with a 15.8 (95% confidence limits [CL]: 5.5-48.8) relative risk of being infected. In infected infants aged 5 months a decrease in these parameters was associated with an 11.2 (95% CL: 1.6-77.8) relative risk of developing eventual severe clinical outcome. Low RBC counts, Hb concentrations, and hematocrit values may be included among predictive criteria in infants of HIV-1 infected mothers.
Pediatr AIDS HIV Infect 1995 Dec
PMID:Hemochrome parameters during the first two years of life in children with perinatal HIV-1 infection. 1136 57

There is accumulating evidence that the marrow-failure of myelodysplastic syndrome (MDS) is immune-mediated. We studied patients with MDS to look for oligoclonal or clonal expansion in T cells indicative of an autoimmune process. We used a PCR-based technique (spectratyping) to characterize the T cell repertoire in MDS (n=15; 9 RA, 4 RARS, 2 RAEB) and compared results with age-matched healthy donors (n=20) and transfusion-dependent (TD) patients with hemoglobinopathy (n=5). We found a significantly higher number of skewed Vbeta profiles in the MDS patients compared with controls. In peripheral blood T cells, 60/345 Vbeta profiles examined were skewed in MDS patients compared with 3/115 Vbeta profiles in TD controls (P<0.0001), and 58/460 Vbeta profiles in age-matched controls (P=0.05). A study of Jbeta region within the skewed Vbeta profiles revealed preferential usage of Jbeta 2.1 in MDS in contrast with a wide distribution over the entire Jbeta spectrum in controls, consistent with non-random T cell clonal expansion in MDS. These findings provide further evidence that T cell mediated immune processes are a feature of MDS.
Leuk Res 2001 Dec
PMID:Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. 1168 79

Although most of the diagnostic applications of flow cytometry bring forth examples of leukocyte immunophenotyping for immunodeficiency diseases and leukemia-lymphoma diagnosis, the same technology has improved medical assessment of diseases affecting the red cell and erythropoiesis. Flow cytometric methods were first applied to laboratory hematology with the improvement in reticulocyte counting and the creation of the immature reticulocyte fraction for better anemia evaluation and therapeutic monitoring. A more recent improvement attributable to flow cytometry is accurate detection of fetal red cells in the evaluation of FMH hemorrhage. The same method used in the detection of fetal RBCs based on HbF content measurement using monoclonal antibodies also offers the potential for enumeration of F cells, which promises to have use in therapeutic monitoring of patients with sickle cell disease and the evaluation of other hemoglobinopathies and myelodysplasia. Other clinical uses of flow cytometric RBC analysis include nonisotopic red cell survival studies, sensitive blood group typing, sensitive detection of immune-mediated hemolytic diseases, and evaluation of parasitic diseases whose life cycle involves intracellular RBC infestation. This article summarizes red cell flow cytometry, particularly as it impacts the areas of immunohematology and laboratory hematology, and points to areas of potential future contribution of this technology to diagnostic medicine.
Clin Lab Med 2001 Dec
PMID:Diagnostic utility of red cell flow cytometric analysis. 1177 Feb 90

Screening the hearing of all newborns, both NICU and well nursery, is rapidly becoming the standard of care. The impetus for universal newborn hearing screening (UNHS) has come from outside the domain of nursing and the newborn nursery. Because nursing will be involved in nearly all aspects of UNHS, nurses need a thorough knowledge base about permanent childhood hearing loss (PCHL) and UNHS. Technology exisits today that can objectively and physiologically screen for this condition at a cost comparable to metabolic screening. PCHL occurs more than twice as often as all the hemoglobinopathies and inborn errors of metabolism combined. Undiagnosed hearing loss often leads to permanent developmental delays. The ultimate goal of early diagnosis and intervention for a congenital hearing loss is to enable the child to develop language and communication skills that correspond to his chronological age and innate cognitive abilities.
Neonatal Netw 2001 Dec
PMID:Universal newborn hearing screening coming soon: "hear's" why. 1214 1

Intravascular hemolysis is associated with several pathologic conditions that include hemoglobinopathies, trauma, malaria, and bacterial infections. Among plasma-protective proteins against oxidative damage caused by red blood cell rupture, haptoglobin and hemopexin are thought to play a crucial role. Haptoglobin and hemopexin, by binding with high-affinity hemoglobin and heme, respectively, exert an antioxidant action by preventing heme-catalyzed free radical production. Moreover, these proteins prevent iron loss by inhibiting glomerular filtration of hemoglobin and heme diffusion through plasma membranes. Analysis of single-null mice demonstrated the antioxidant action of haptoglobin and hemopexin in vivo and suggests that the 2 proteins cooperate in the resolution of hemolytic stress. To evaluate the physiological relevance of the haptoglobin-hemopexin system and the principal targets of its action, we generated haptoglobin-hemopexin double-knockout mice and analyzed them under basal conditions and after acute hemolysis. Whereas haptoglobin-hemopexin double-null mice displayed no obvious alteration in phenotype under basal conditions, nonlethal hemolytic stress in these animals led to pronounced splenomegaly as well as liver inflammation and fibrosis. These data demonstrate that haptoglobin and hemopexin together are essential for protection from splenomegaly and liver fibrosis resulting from intravascular hemolysis.
Blood 2002 Dec 01
PMID:Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis. 1239 71

Orally bioactive compounds that induce gamma globin gene expression at tolerable doses are needed for optimal treatment of the beta-hemoglobinopathies. Short-chain fatty acids (SCFAs) of 2 to 6 carbons in length induce gamma globin expression in animal models, and butyrate, phenylbutyrate, and valproate induce gamma globin in human patients. The usefulness of these compounds, however, is limited by requirements for large doses because of their rapid metabolism and their tendency to inhibit cell proliferation, which limits the pool of erythroid progenitors in which gamma globin can be induced. Selected short-chain fatty acid derivatives (SCFADs) were recently found to induce gamma globin and to stimulate the proliferation of hematopoietic cells in vitro. These SCFADs are now evaluated in vivo in nonanemic transgenic mice containing the human beta globin gene locus and in anemic phlebotomized baboons. In mice treated with a SCFAD once daily for 5 days, gamma globin mRNA increased 2-fold, reticulocytes increased 3- to 7-fold, and hematocrit levels increased by 27%. Administration of 3 SCFADs in anemic baboons increased F-reticulocytes 2- to 15-fold over baseline and increased total hemoglobin levels by 1 to 2 g/dL per week despite ongoing significant daily phlebotomy. Pharmacokinetic studies demonstrated 90% oral bioavailability of 2 SCFADs, and targeted plasma levels were maintained for several hours after single oral doses equivalent to 10% to 20% of doses required for butyrate. These findings identify SCFADs that stimulate gamma globin gene expression and erythropoiesis in vivo, activities that are synergistically beneficial for treatment of the beta hemoglobinopathies and useful for the oral treatment of other anemias.
Blood 2002 Dec 15
PMID:Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo. 1239 83

Reactivation of fetal hemoglobin genes has been proposed as a potential therapeutic procedure in patients with beta-thalassemia, sickle cell disease, or other beta-hemoglobinopathies. In vitro model systems based on small plasmid globin gene constructs have previously been used in human and mouse erythroleukemic cell lines to study the molecular mechanisms regulating the expression of the fetal human globin genes and their reactivation by a variety of pharmacologic agents. These studies have led to great insights in globin gene regulation and the identification of a number of potential inducers of fetal hemoglobin. In this study we describe the development of enhanced green fluorescence protein (EGFP) reporter systems based on bacterial artificial chromosomes (EBACs) to monitor the activity of the epsilon-, (G)gamma-, (A)gamma-, delta-, and beta-globin genes in the beta-globin locus. Additionally, we demonstrate that transfection of erythroleukemia cells with our EBACs is greatly enhanced by expression of EBNA1, which also facilitates episomal maintenance of our constructs in human cells. Our studies in human cells have shown physiologically relevant differences in the expression of each of the globin genes and also demonstrate that hemin is a potent inducer of EGFP expression from EGFP-modified epsilon-, (G)gamma-, and (A)gamma-globin constructs. In contrast, the EGFP-modified delta- and beta-globin constructs consistently produced much lower levels of EGFP expression on hemin induction, mirroring the in vivo ontogeny. The EGFP-modified beta-globin eukaryotic BAC (EBAC) vector system can thus be used in erythroleukemia cells to evaluate induction of the epsilon- and gamma-globin genes from the intact human beta-globin locus.
Blood 2002 Dec 01
PMID:Development of sensitive fluorescent assays for embryonic and fetal hemoglobin inducers using the human beta -globin locus in erythropoietic cells. 1239 13


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