Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past five years have seen numerous advances in the field of pediatric infectious diseases, and many of these have a substantial impact on the practice of dermatology. We review some of these advances and discuss their implications on etiology, diagnosis, therapy and complications of some relatively common conditions. The etiologic agent of exanthum subitum (roseola infantum) has been clearly implicated as a herpesvirus-6. Although in the classically described situation high fever in a young child is followed by defervescence and rash, two new scenarios have been described associated with this virus. The first is fever without rash and the second is rash without fever. The etiologic agent of erythema infectiosum ("slapped cheek") has been shown to be a human parvovirus B19. The virus has also been associated with aplastic crises (in hemoglobinopathies), hydrops fetalis, and a syndrome of subacute arthralgias in women. The etiologic agent in cat-scratch disease has recently been shown to be a small pleomorphic bacillus that also can produce pyogenic granuloma-like lesions in patients with acquired immunodeficiency syndrome. The number of cases of congenital syphilis, particularly in large cities, is increasing tremendously. Many of these infants have received no prenatal care because of drug abuse problems in their parents. Finally, we describe the changing etiology of impetigo that is predominantly associated with Staphylococcus aureus. We further describe the growing resistance to erythromycin and several new erythromycin drug-drug interactions.
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PMID:Recent advances in pediatric infectious diseases and their impact on dermatology. 206 33

The diverse manifestations of human parvovirus B19 infection have been well established. Erythema infectiosum, fetal hydrops, adult arthropathy, and aplastic anemia in patients with hemoglobinopathies or underlying immunocompromise have been described. Recently we successfully treated a patient who, after heart transplantation, had fever, rash, and pneumonia with respiratory failure caused by human parovirus B19. Human parovirus B19 has not been reported previously as a pathogen causing pulmonary disease after pediatric heart transplantation, and we wish to report it at this time.
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PMID:Severe pneumonia after heart transplantation as a result of human parvovirus B19. 803 18

The pathogenic human parvovirus B19 is an autonomously replicating virus with a remarkable tropism for human erythroid progenitor cells. Although the target cell specificity for B19 infection has been suggested to be mediated by the erythrocyte P-antigen receptor (globoside), a number of nonerythroid cells that express this receptor are nonpermissive for B19 replication. To directly test the role of expression from the B19 promoter at map unit 6 (B19p6) in the erythroid cell specificity of B19, we constructed a recombinant adeno-associated virus 2 (AAV), in which the authentic AAV promoter at map unit 5 (AAVp5) was replaced by the B19p6 promoter. Although the wild-type (wt) AAV requires a helper virus for its optimal replication, we hypothesized that inserting the B19p6 promoter in a recombinant AAV would permit autonomous viral replication, but only in erythroid progenitor cells. In this report, we provide evidence that the B19p6 promoter is necessary and sufficient to impart autonomous replication competence and erythroid specificity to AAV in primary human hematopoietic progenitor cells. Thus, expression from the B19p6 promoter plays an important role in post-P-antigen receptor erythroid-cell specificity of parvovirus B19. The AAV-B19 hybrid vector system may also prove to be useful in potential gene therapy of human hemoglobinopathies.
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PMID:Parvovirus B19 promoter at map unit 6 confers autonomous replication competence and erythroid specificity to adeno-associated virus 2 in primary human hematopoietic progenitor cells. 861 12

Anemia, mental status changes, and fatal respiratory failure complicated a febrile illness in a previously healthy 14-year-old black female. At autopsy, widespread fat emboli and bone marrow necrosis were found. Hemoglobin electrophoresis on an antemortem, pretransfusion specimen revealed hemoglobin S/beta+ thalassemia. Acute parvovirus B19 (PV B19) infection was suspected. Postmortem serum and a variety of paraffin-embedded tissues were assayed for PV B19 DNA using the polymerase chain reaction (PCR). The expected PCR product was identified in the serum specimen and in paraffin-embedded sections of bone marrow, kidney, spleen, parathyroid, thyroid, adrenal, and gastrointestinal tract: lung, liver, ovary, fallopian tube, uterus, brain, heart, and pancreas were negative. PV B19 infection is highly contagious and may be rapidly fatal in children with hemoglobinopathies by several mechanisms, including fat embolism. Therefore, there exists the risk of multiple deaths within a family. The acute infection may be easily and expeditiously diagnosed using serum or a variety of paraffin-embedded tissues.
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PMID:Fatal fat embolism syndrome in a child with undiagnosed hemoglobin S/beta+ thalassemia: a complication of acute parvovirus B19 infection. 896 32

Human parvovirus B19 gene expression from the viral p6 promoter (B19p6) is restricted to primary human hematopoietic cells undergoing erythroid differentiation. We have demonstrated that expression from this promoter does not occur in established human erythroid cell lines in the context of a recombinant parvovirus genome (Ponnazhagan et al. J Virol 69:8096-8101, 1995). However, abundant expression from this promoter can be readily detected in primary human bone marrow cells (Wang et al. Proc Natl Acad Sci USA 92:12416-12420, 1995; Ponnazhagan et al. J Gen Virol 77:1111-1122, 1996). In the present studies, we investigated the pattern of expression from the B19p6 promoter in primary human bone marrow-derived CD34+ HPC undergoing differentiation into myeloid and erythroid lineages. CD34+ cells were transduced with recombinant adeno-associated virus 2 (AAV) vectors containing the beta-galactosidase (lacZ) gene under the control of the following promoters/enhancers: the cytomegalovirus promoter (vCMVp-lacZ), B19p6 promoter (vB19p6-lacZ), B19p6 promoter with an upstream erythroid cell-specific enhancer element (HS-2) from the locus control region (LCR) from the human beta-globin gene cluster (vHS2-B19p6-lacZ), and the human beta-globin gene promoter with the HS-2 enhancer (vHS2-beta p-lacZ). Transgene expression was evaluated either 48 h after infection or following erythroid differentiation in vitro for 3 weeks. Whereas high-level expression from the CMV promoter 48 h after infection diminished with time, low-level expression from the B19p6 and the beta-globin promoters increased significantly following erythroid differentiation. Furthermore, in HPC assays, there was no significant difference in the level of expression from the CMV promoter in myeloid or erythroid cell-derived colonies. Expression from the B19p6 and the beta-globin promoters, on the other hand, was restricted to erythroid cell colonies. These data further corroborate that the B19p6 promoter is erythroid cell-specific and suggest that the recombinant AAV-B19 hybrid vectors may prove useful in gene therapy of human hemoglobinopathies in general and sickle cell anemia and beta-thalassemia in particular.
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PMID:Adeno-associated virus 2-mediated transduction and erythroid lineage-restricted expression from parvovirus B19p6 promoter in primary human hematopoietic progenitor cells. 1064 62

This review summarizes state-of-the-art and emerging techniques in the antenatal diagnosis of fetal anemia and hemoglobinopathies. Fetal anemia may result from hemolytic disease, hemorrhage, suppression of erythropoiesis, infection (eg, parvovirus B19), or trauma. The clinical laboratory plays an essential role in the evaluation of these disorders by way of the use of various hematologic, biochemical, serologic, cytometric, and molecular genetics methods. Hemoglobinopathies are the most common class of single gene disorders worldwide. The authors have used the example of homozygous alpha-thalassemia major (Hb Barts disease) as a paradigmatic case for antenatal hemoglobinopathy screening. Perhaps the most familiar indication for hematologic screening in pregnancy is HDFN, most commonly in pregnancies previously sensitized to the RhD antigen. All pregnant women, regardless of their past medical or obstetric history or previous antibody screens, should have ABO/Rh blood typing and a red cell antibody screen performed at the first prenatal visit. Long-established methods for assaying FMH (KB method), microcytosis (hemogram with red cell indices), and blood group incompatibility (direct antigen test, serologies) remain critical for rapid, sensitive diagnosis. Analysis of fetal free DNA in maternal plasma holds the promise for rapid, ultrasensitive, and noninvasive detection of many fetal hematologic disorders.
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PMID:Testing for hematologic disorders and complications. 1284 47

The records of 22 children with parvovirus B19-induced aplastic crisis were reviewed. The group consisted of 16 children with sickle cell hemoglobinopathies and 6 with hereditary spherocytosis. Children presented to the hospital 0.5 to 8 days (mean, 2.4 days) after the onset of symptoms. The children with sickle-cell disease presented earlier (mean, 1.4 days) than did children with hereditary spherocytosis (mean, 5 days; P = 0.02. Fever was the most common symptom, occurring in 73% of children. Rash did not occur in either group. Reticulocyte counts began to rise 1 week after onset of illness associated with a rise in parvovirus B19-specific IgG antibody. These data suggest that parvovirus B19 infection in children with sickle-cell hemoglobinopathies and heredity spherocytosis differs from infection in normal children.
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PMID:Clinical presentation of parvovirus B19 infection in children with aplastic crisis. 1468 75

Recent reports suggested that parvovirus B19 (B19) might persist in immunocompetent individuals such as blood donors, but only cross-sectional data were available. Serial samples from a cohort of multitransfused patients with hemoglobinopathies and a cross-sectional population of pregnant women were tested for B19 markers. Of 76 red cell recipients, 6 (8%) had persistent viral DNA for 1 to 3 or more years, depending on the sensitivity of the genomic amplification assay. All patients also carried B19-specific immunoglobulin G (IgG). In contrast, 0.8% of 500 pregnant women carried both detectable B19 DNA and specific IgG. These results demonstrate that persistence of low levels of B19 DNA suggested by cross-sectional studies is frequent in multitransfused patients and that the virus may remain detectable several years after infection in nonimmunodeficient individuals.
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PMID:Persistent B19 infection in immunocompetent individuals: implications for transfusion safety. 1597 79

The clinical approach to thalassemia and hemoglobinopathies, specifically Sickle Cell Disease (SCD), based on transfusions, iron chelation and bone marrow transplantation has ameliorated their prognosis. Nevertheless, infections still may cause serious complications in these patients. The susceptibility to infections in thalassemia and SCD arises both from a large spectrum of immunological abnormalities and from exposure to specific infectious agents. Four fundamental issues will be focused upon as central causes of immune dysfunction: the diseases themselves; iron overload, transfusion therapy and the role of the spleen. Thalassemia and SCD differ in their pathogenesis and clinical course. It will be outlined how these differences affect immune dysfunction, the risk of infections and the types of most frequent infections in each disease. Moreover, since transfusions are a fundamental tool for treating these patients, their safety is paramount in reducing the risks of infections. In recent years, careful surveillance worldwide and improvements in laboratory tests reduced greatly transfusion transmitted infections, but the problem is not completely resolved. Finally, selected topics will be discussed regarding Parvovirus B19 and transfusion transmitted infections as well as the prevention of infectious risk postsplenectomy or in presence of functional asplenia.
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PMID:Infections in thalassemia and hemoglobinopathies: focus on therapy-related complications. 2141 96

Alloimmunity in pregnancy is the basis for two of the major complications of pregnancy in transfusion medicine: hemolytic disease of the fetus and newborn (HDFN), and fetal and neonatal alloimmune thrombocytopenia (FNAIT). Use of Rh(D) immune globulin has dramatically reduced the incidence of HDFN in Rh(D)-mismatched pregnancies. Treatment of HDFN may involve intrauterine transfusion, with fetal and neonatal survival rates of 70% to 90%. Treatments for FNAIT include immune globulin, steroids, or in severe cases, intrauterine platelet transfusions. Transfusion medicine is central to the management of pregnancy-associated complications such as postpartum hemorrhage, parvovirus B19 infection, hemoglobinopathies, and aplastic anemia.
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PMID:Transfusion medicine and the pregnant patient. 2144 37


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